Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Roles of Leptin in Cancer Progression

  • Kang, Yu-Jin (College of Pharmacy, Duksung Women's University) ;
  • Moon, A-Ree (College of Pharmacy, Duksung Women's University)
  • Received : 2010.09.27
  • Accepted : 2010.10.13
  • Published : 2010.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Growing evidence suggests a prominent role for leptin in human cancer progression. The intricate pattern of leptin cross-talk with other associated signaling pathways is a critical area of research that will ultimately contribute to comprehending the role of leptin in cancer progression. This review summarizes a portion of the current understanding of leptin signaling, with a critical focus on its contribution to tumor cell invasion and metastasis. Five topics are addressed in this review: (1) Leptin receptor, (2) Leptin signaling, (3) Leptin and cancer, and (4) Leptin and tumor invasion. Due to the complex cellular effects of leptin, a more precise understanding of leptin signaling pathways must still be elucidated. Leptin is clearly a major factor for stimulating tumor progression through a complex spectrum of interplay and cross-talk among various signaling molecules. An understanding of the role of leptin in invasion and metastasis will provide valuable information for establishing strategies to modulate leptin signaling, which should be a high priority for the development of anti-cancer therapeutics.

Keywords

References

  1. Ahima, R. S. and Flier, J. S. (2000). Adipose tissue as anendocrine organ. Trends Endocrinol. Metab. 11, 327-332. https://doi.org/10.1016/S1043-2760(00)00301-5
  2. Attoub, S., Noe, V., Pirola, L., Bruyneel, E., Chastre, E., Mareel,M., Wymann, M. P. and Gespach, C. (2000). Leptin promotesinvasiveness of kidney and colonic epithelial cells via phosphoinositide3-kinase-, Rho-, and Rac-dependent signalingpathways. FASEB J. 14, 2329-2338. https://doi.org/10.1096/fj.00-0162
  3. Banks, A. S., Davis, S. M., Bates, S. H. and Myers, M. G. (2000).Activation of downstream signals by the long form of theleptin receptor. J. Biol. Chem. 275, 14563-14572. https://doi.org/10.1074/jbc.275.19.14563
  4. Bauer, K. R., Brown, M., Cress, R. D., Parise, C. A. andCaggiano, V. (2007). Descriptive analysis of estrogen receptor(ER)‐negative, progesterone receptor (PR)-negative, andHER2-negative invasive breast cancer, the so-called triplenegativephenotype. Am. Can. Soc. 109, 1721-1728.
  5. Baumann, H., Morella, K. K., White, D. W., Dembski, M., Bailon,P. S., Kim, H., Lai, C. F. and Tartaglia, L. A. (1996). The fulllengthleptin receptor has signaling capabilities of interleukin6-type cytokine receptors. Proc. Natl. Acad. Sci. USA. 93,8374-8378. https://doi.org/10.1073/pnas.93.16.8374
  6. Bjorbaek, C., Uotani, S., da Silva, B. and Flier, J. S. (1997).Divergent signaling capacities of the long and short isoformsof the leptin recptor. J. Biol. Chem. 272, 32686-32695. https://doi.org/10.1074/jbc.272.51.32686
  7. Bjorbaek, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E. andFlier, J. S. (1998). Identification of SOCS-3 as a potentialmediator of central leptin resistance. Mol. Cell 1, 619-625. https://doi.org/10.1016/S1097-2765(00)80062-3
  8. Bjorbaek, C., El-Haschimi, K., Frantz, J. D. and Flier, J. S. (1999).The role of SOCS-3 in leptin signaling and leptin resistance.J. Biol. Chem. 274, 30059-30065. https://doi.org/10.1074/jbc.274.42.30059
  9. Bjorbaek, C., Buchholz, R. M., Davis, S. M., Bates, S. H.,Pierroz, D. D., Gu, H., Neel, B. G., Myers, M. G. and Flier, J.S. Jr. (2001). Divergent roles of SHP-2 in ERK activation byleptin receptors. J. Biol. Chem. 276, 4747-4755. https://doi.org/10.1074/jbc.M007439200
  10. Blum, W. F., Englaro, P., Hanitsch, S., Juul, A., Hertel, N. T.,Muller, J., Skakkebaek, N. E., Heiman, M. L., Birkett, M.,Attanasio, A. M., Kiess, W. and Rascher, W. (1997). Plasma leptin levels in healthy children and adolescents: Dependenceon body mass index, body fat mass, gender, pubertal stage,and testosterone. J. Clin. Endocrinol. Metab. 82, 2904-2910 https://doi.org/10.1210/jc.82.9.2904
  11. Borugian, M. J., Sheps, S. B., Kim-Sing, C., Olivotto, I. A., VanPatten, C., Dunn, B. P., Coldman, A. J., Potter, J. D.,Gallagher, R. P. and Hislop, T. G. (2003). Waist-to-hip ratioand breast cancer mortality. Am. J. Epidemiol. 158, 963-968. https://doi.org/10.1093/aje/kwg236
  12. Bouloumie, A., Drexler, H. C., Lafontan, M. and Busse, R.(1998). Leptin, the product of Ob gene, promotes angiogenesis.Circ. Res. 83, 1059-1066. https://doi.org/10.1161/01.RES.83.10.1059
  13. Briscoe, C. P., Hanif, S., Arch, J. R. and Tadayyon, M. (2001).Fatty acids inhibit leptin signalling in BRIN-BD11 insulinomacells. J. Mol. Endocrinol. 26, 145-154. https://doi.org/10.1677/jme.0.0260145
  14. Cao, R., Brakenhielm, E., Wahlestedt, C., Thyberg, J. and Cao,Y. (2001). Leptin induces vascular permeability and synergisticallystimulates angiogenesis with FGF-2 and VEGF.Proc. Natl. Acad. Sci. USA. 98, 6390-6395. https://doi.org/10.1073/pnas.101564798
  15. Casabiell, S., Pineiro, V., Peino, R., Lage, M., Camina, J.,Gallego, R., Vallego, L. G., Dieguez, C. and Casanueva, F.F. (1998). Gender differences in both spontaneous andstimulated leptin secretion by human omental adipose tissuein vitro: Dexamethasone and estradiol stimulate leptinrelease in women, but not in men. J. Clin. Endocrinol. Metab.83, 2149-2155. https://doi.org/10.1210/jc.83.6.2149
  16. Castellucci, M., Matteis, R., De Meisser, A., Cancello, R.,Monsurro, V., Islami, D., Sarzani, R., Marzioni, D., Cinti, S.and Bischof, P. (2000). Leptin modulates extracellular matrixmolecules and metalloproteinases: possible implications fortrophoblast invasion. Mol. Hum. Reprod. 6, 951-958. https://doi.org/10.1093/molehr/6.10.951
  17. Castracane, V. D., Kraemer, R. R., Franken, M. A., Kraemer, G.R. and Gimpel, T. (1998). Serum leptin concentration inwomen: Effect of age, obesity, and estrogen administration.Fertil. Steril. 70, 472-477. https://doi.org/10.1016/S0015-0282(98)00187-3
  18. Catalano, S., Marsico, S., Giordano, C., Mauro, L., Rizza, P.,Panno, M. L. and Ando, S. (2003). Leptin enhances, via AP-1,expression of aromatase in the MCF-7 cell line. J. Biol.Chem. 278, 28668-28676. https://doi.org/10.1074/jbc.M301695200
  19. Chlebowski, R. T., Aiello, E. and McTiernan, A. (2002). Weightloss in breast cancer patient management. J. Clin. Oncol. 20,1128-1143. https://doi.org/10.1200/JCO.20.4.1128
  20. Choi, J. H., Park, S. H., Leung, P. C. and Choi, K. C. (2004).Expression of leptin receptors and potential effects of leptinon the cell growth and activation of mitogen-activated proteinkinases in ovarian cancer cells. J. Clin. Endocrinol. Metab.90, 207-210. https://doi.org/10.1210/jc.2004-0297
  21. Cioffi, J. A., Shafer, A. W., Zupancic, T. J., Smith-Gbur, J.,Mikhail, A., Platika, D. and Snodgrass, H. R. (1996). NovelB219/OB receptor isoforms: possible role of leptin inhematopoiesis and reproduction. Nat. Med. 2, 585-589. https://doi.org/10.1038/nm0596-585
  22. Cirillo, D., Rachiglio, A. M., La Montagna, R., Giordano, A. andNormanno, N. (2008). Leptin signaling in breast cancer: anoverview. J. Cell. Biochem. 105, 956-964. https://doi.org/10.1002/jcb.21911
  23. Cleary, M. P. and Maihle, N. J. (1997). The role of body massindex in the relative risk of developing premenopausalversus postmenopausal breast cancer. Proc. Soc. Exp. Biol.Med. 216, 28-43. https://doi.org/10.3181/00379727-216-44153B
  24. Cleary, M. P., Phillips, F. C., Getzin, S. C., Jacobson, T. L.,Jacobson, M. K., Christensen, T. A., Juneja, S. C., Grande,J. P. and Maihle, N. J. (2003). Genetically obese MMTVTGF-alpha/Lep(ob)Lep(ob) female mice do not developmammary tumors. Breast Cancer Res. Treat. 77, 205-215. https://doi.org/10.1023/A:1021891825399
  25. Cohen, B., Novick, D. and Rubinstein, M. (1996). Modulation ofinsulin activities by leptin. Science 274, 1185-1188. https://doi.org/10.1126/science.274.5290.1185
  26. Cusin, I., Sainsbury, A., Doyle, P., Rohner-Jeanrenaud, F. andJeanrenaud, B. (1995). The ob gene and insulin. A relationshipleading to clues to the understanding of obesity.Diabetes 44, 1467-1470. https://doi.org/10.2337/diabetes.44.12.1467
  27. Dagogo-Jack, S., Selke, G., Melson, A. K. and Newcomer, J. W.(1997). Robust leptin secretory responses to dexamethasonein obese subjects. J. Clin. Endocrinol. Metab. 82, 3230-3233. https://doi.org/10.1210/jc.82.10.3230
  28. Devos, R., Guisez, Y., Van der Heyden, J., White, D. W., Kalai,M., Fountoulakis, M. and Plaetinck, G. (1997). Ligandindependentdimerization of the extracellular domain of theleptin receptor and determination of the stoichiometry ofleptin binding. J. Biol. Chem. 272, 18304-18310. https://doi.org/10.1074/jbc.272.29.18304
  29. De Vos, P., Saladin, R., Auwerx, J. and Staels, B. (1995). Inductionof ob gene expression by corticosteroids is accompaniedby body weight loss and reduced food intake. J. Biol. Chem.270, 15958-15961. https://doi.org/10.1074/jbc.270.27.15958
  30. Dieudonne, M. N., Machinal-Quelin, F., Serazin-Leroy, V.,Leneveu, M. C., Pecquery, R. and Giudicelli, Y. (2002).Leptin mediates a proliferative response in human MCF7breast cancer cells. Biochem. Biophys. Res. Commun. 293,622-628. https://doi.org/10.1016/S0006-291X(02)00205-X
  31. Eisemberg, A., Biener, E., Charlier, M., Krishnan, R. V., Dijane,J., Herman, B. and Gertler, A. (2004). Transactivation oferbB2 by short and long isoforms of leptin receptors. FEBSLett. 565, 139-142. https://doi.org/10.1016/j.febslet.2004.03.089
  32. Elbers, J. M., Asscheman, H., Seidell, J. C., Frolich, M., Meinders,A. E. and Gooren, L. J. (1997). Reversal of the sexdifference in serum leptin levels upon cross-sex hormoneadministration in transsexuals. J. Clin. Endocrinol. Metab.82, 3267-3270. https://doi.org/10.1210/jc.82.10.3267
  33. Ellis, L. M. and Fidler, I. J. (1996) Angiogenesis and metastasis.Eur. J. Cancer 32A, 2451-2460.
  34. Enger, S. M., Ross, R. K., Paganini-Hill, A., Carpenter, C. L. andBernstein, L. (2000). Body size, physical activity, and breastcancer hormone receptor status: Results from two casecontrolstudies. Cancer Epidemiol. Biomarkers. Prev. 9,681-687.
  35. Fain, J. N., Leffler, C. W. and Bahouth, S. W. (2000). Eicosanoidsas endogenous regulators of leptin release andlipolysis by mouse adipose tissue in primary culture. J. Lipid.Res. 41, 1689-1694.
  36. Fidler, I. J. (1990). Critical factors in the biology of humancancer metastasis. Cancer Res. 50, 6130-6138.
  37. Fiorio, A., Mercanti, A., Terrasi, M., Micciolo, R., Remo, A.,Auriemma, A., Molino, A., Parolin, V., Di Stefano, B., Bonetti,F., Giordano, A., Cetto, G. L. and Surmacz, E. (2008).Leptin/HER2 crosstalk in breast cancer: in vitro study andpreliminary in vivo anlysis. BMC Cancer 8, 305-315. https://doi.org/10.1186/1471-2407-8-305
  38. Folkman, J. (1995). Angiogenesis in cancer, vascular, rheumatoidand other disease. Nat. Med. 1, 27-31. https://doi.org/10.1038/nm0195-27
  39. Fong, T. M., Huang, R. R., Tota, M. R., Mao, C., Smith, T.,Varnerin, J., Karpitskiy, V. V., Krause, J. E. and Van derPloeg, L. H. (1998). Localization of leptin binding domain inthe leptin receptor. Mol. Pharmacol. 53, 234-240. https://doi.org/10.1124/mol.53.2.234
  40. Frankenberry, K. A., Somasundar, P., McFadden, D. W. andVona-Davis, L. C. (2004). Leptin induces cell migration andthe expression of growth factors in human prostate cancercells. Am. J. Surg. 188, 560-565. https://doi.org/10.1016/j.amjsurg.2004.07.031
  41. Gainsford, T., Wilson, T. A., Metcalf, D., Handman, E., McFarlane,C., Ng, A., Alexander, W. S. and Hilton, D. J. (1996). Leptincan induce proliferation, differentiation, functional activationof hemopoietic cells. Proc. Natl. Acad. Sci. USA. 93,14564-14568. https://doi.org/10.1073/pnas.93.25.14564
  42. Garofalo, C., Sisci, D. and Surmacz, E. (2004). Leptin interfereswith the effects of the antiestrogen ICI 182,780 in MCF-7breast cancer cells. Clin. Cancer Res. 10, 6466-6475. https://doi.org/10.1158/1078-0432.CCR-04-0203
  43. Garofalo, C. and Surmacz, E. (2006). Lepin and cancer. J. CellPhysiol. 207, 12-22. https://doi.org/10.1002/jcp.20472
  44. Garofalo, C., Koda, M., Cascio, S., Sulkowska, M., Kanczuga-Koda, L., Golaszewska, J., Russo, A., Sulkowski, S. andSurmacz, E. (2006). Increased expression of leptin and theleptin receptor as a marker of breast cancer progression:Possible role of obesity-related stimuli. Clin. Cancer Res. 12,1447-1453. https://doi.org/10.1158/1078-0432.CCR-05-1913
  45. Ghilardi, N., Ziegler, S., Wiestner, A., Stoffel, R., Heim, M. H.and Skoda, R. C. (1996). Defective STAT signaling by theleptin receptor in diabetic mice. Proc. Natl. Acad. Sci. USA.93, 6231-6235. https://doi.org/10.1073/pnas.93.13.6231
  46. Glasow, A., Bornstein, S. R, Chrousos, G. P., Brown, J. W andScherbaum, W. A. (1999). Detection of Ob-receptor inhuman adrenal neoplasms and effect of leptin on adrenal cellproliferation. Horm. Metab. Res. 31, 247-251. https://doi.org/10.1055/s-2007-978726
  47. Gonzalez, R. R., Cherfils, S., Escobar, M., Yoo, J. H., Carino,C., Styer, A. K., Sullivan, B. T., Sakamoto, H., Olawaiye, A.,Serikawa, T., Lynch, M. P. and Rueda, B. R. (2006). Leptinsignaling promotes the growth of mammary tumors andincreases the expression of vascular endothelial growthfactor (VEGF) and its receptor type two (VEGF-R2). J. Biol.Chem. 281, 26320-26328. https://doi.org/10.1074/jbc.M601991200
  48. Han, C., Zhang, H. T., Du, L., Liu, X., Jing, J., Zhao, X., Yang, X.and Tian, B. (2005). Serum levels of leptin, insulin, and lipidsin relation to breast cancer in China. Endocrine 26, 19-24. https://doi.org/10.1385/ENDO:26:1:019
  49. Hardwick, J. C., Van Den Brink, G. R., Offerhaus, G. J., VanDeventer, S. J. and Peppelenbosch, M. P. (2001). Leptin is agrowth factor for colonic epithelial cells. Gastroenterology121, 79-90. https://doi.org/10.1053/gast.2001.25490
  50. Harvie, M., Hooper, L. and Howell, A. H. (2003). Central obesityand breast cancer risk: A systematic review. Obes. Rev. 4,157-173. https://doi.org/10.1046/j.1467-789X.2003.00108.x
  51. Hileman, S. M., Tornoe, J., Flier, J. S. and Bjorbaek, C. (2000).Transcellular transport of leptin by the short leptin receptorisoform ObRa in madin-darby canine kidney cells. Endocrinology141, 1955-1966. https://doi.org/10.1210/en.141.6.1955
  52. Hino, M., Nakao, T., Yamane, T., Ohta, K., Takubo, T. andTatsumi, N. (2000). Leptin receptor and leukemia. Leuk.Lymphoma 36, 457-461. https://doi.org/10.3109/10428190009148392
  53. Hu, X., Juneja, S. C., Maihle, N. J. and Cleary, M. P. (2002).Leptin induces, via ERK1/ERK2 signal, functional activationof estrogen receptor a in MCF-7 cells. J. Natl. Cancer. Inst.94, 1704-1711. https://doi.org/10.1093/jnci/94.22.1704
  54. Huang, L., Wang, Z. and Li, C. (2001). Modulation of circulatingleptin levels by its　soluble receptor. J. Biol. Chem. 276,6343-6349. https://doi.org/10.1074/jbc.M009795200
  55. Huang, W. Y., Newman, B., Millikan, R. C., Schell, M. J., Hulka,B. S. and Moorman, P. G. (2000). Hormone-related factorsand risk of breast cancer in relation to estrogen receptor andprogesterone receptor status. Am. J. Epidemiol. 151, 703-714. https://doi.org/10.1093/oxfordjournals.aje.a010265
  56. Hynes, G. R. and Jones, P. J. (2001). Leptin and its role in lipidmetabolism. Curr. Opin. Lipidol. 12, 321-327. https://doi.org/10.1097/00041433-200106000-00012
  57. Ishikawa, M., Kitayama, J. and Nagawa, H. (2004). Enhancedexpression of leptin and leptin receptor (OB-R) in humanbreast cancer. Clin. Cancer Res. 10, 4325-4331. https://doi.org/10.1158/1078-0432.CCR-03-0749
  58. Islam, M. S., Morton, N. M., Hansson, A. and Emilsson, V.(1997). Rat insulinoma-derived pancreatic beta-cells expressa functional leptin receptor that mediates a proliferativeresponse. Biochem. Biophys. Res. Commun. 238, 851-855. https://doi.org/10.1006/bbrc.1997.7399
  59. Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J. and Thun, M.J. (2007). Cancer Statistics, 2007. CA Cancer J. Clin. 57,43-66. https://doi.org/10.3322/canjclin.57.1.43
  60. Jiang, H., Yu, J., Guo, H., Song, H. and Chen, S. (2007).Upregulation of survivin by leptin/STAT3 signaling in MCF-7cells. Biochem. Biophys. Res. Commun. 368, 1-5. https://doi.org/10.1016/j.bbrc.2007.04.004
  61. Jockenhovel, F., Blum, W. F., Vogel, E., Englaro, P., Muller-Wieland, D., Reinwein, D.,　Rascher, W. and Krone, W.(1997). Testosterone substitution normalizes elevated serumleptin levels in hypogonadal men. J. Clin. Endocrinol. Metab.82, 2510-2513. https://doi.org/10.1210/jc.82.8.2510
  62. Kulkarni, R. N., Wang, Z. L., Wang, R. M., Hurley, J. D., Smith,D. M., Ghatei, M. A., Withers, D. J., Gardiner, J. V., Bailey, C.J. and Bloom, S. R. (1997). Leptin rapidly suppresses insulinrelease from insulinoma cells, rat and human islets and, invivo, in mice. J. Clin. Invest. 100, 2729-2736. https://doi.org/10.1172/JCI119818
  63. Kume, K., Satomura, K., Nishisho, S., Kitaoka, E., Yamanouchi,K., Tobiume, S. and Nagayama, M. (2002). Potential role ofleptin in endochondral ossification. J. Histochem. Cytochem.50, 159-169. https://doi.org/10.1177/002215540205000204
  64. Laud, K., Gourdou, I., Pessemesse, L., Peyrat, J. P. and Djiane,J. (2002). Identification of leptin receptors in human breastcancer: Functional activity in the T47-D breast cancer cellline. Mol. Cell Endocrinol. 188, 219-226. https://doi.org/10.1016/S0303-7207(01)00678-5
  65. Leroy, P., Dessolin, S., Villageois, P., Moon, B. C., Friedman, J.M., Ailhaud, G. and Dani, C. (1996). Expression of ob gene inadipose cells. Regulation by insulin. J. Biol. Chem. 271,2365-2368. https://doi.org/10.1074/jbc.271.5.2365
  66. Liotta, L. A. and Stetler-Stevenson, W. G. (1991). Tumorinvasion and metastasis: an imbalance of positive andnegative regulation. Cancer Res. 51, 5054-5059
  67. Liu, Z., Uesaka, T., Watanabe, H. and Kato, N. (2001). High fatdiet enhances colonic cell proliferation and carcinogenesis inrats by elevating serum leptin. Int. J. Oncol. 19, 1009-1014.
  68. Ma, C., Lin, H., Leonard, S. S., Shi, X., Ye, J. and Luo, J. (2003).Overexpression of ErbB2 enhances ethanol-stimulatedintracellular signaling and invasion of human mammaryepithelial and breast cancer cells in vitro. Oncogene 14,5281-5290.
  69. Machinal-Quelin, F., Dieudonne, M. N., Pecquery, R., Leneveu,M. C. and Giudicelli, Y. (2002). Direct in vitro effects ofandrogens and estrogens on ob gene expression and leptinsecretion in human adipose tissue. Endocrine 18, 179-184. https://doi.org/10.1385/ENDO:18:2:179
  70. McMurtry, V., Simeone, A. M., Nieves-Alicea, R. and Tari, A. M.(2009). Leptin utilizes Jun- N-terminal kinases to stimulatethe invasion of MCF-7 breast cancer cells. Clin. Exp.Metastasis 26, 197-204. https://doi.org/10.1007/s10585-008-9231-x
  71. Mix, H., Widjaja, A., Jandl, O., Cornberg, M., Kaul, A., Goke, M.,Beil, W., Kuske, M., Brabant, G., Manns, M. P. and Wagner,S. (2000). Expression of leptin and leptin receptor isoformsin the human stomach. Gut 47, 481-486. https://doi.org/10.1136/gut.47.4.481
  72. Miyazawa-Hoshimoto, S., Takahashi, K., Bujo, H., Hashimoto,N., Yagui, K. and Saito, Y. (2004). The roles of degree of fatdeposition and its localization on VEGF expression inadipocytes. Am. J. Physiol. Endocrinol. Metab. 288, 1128-1136. https://doi.org/10.1152/ajpendo.00003.2004
  73. Moon, H. G., Han, W. and Noh, D. Y. (2009). Underweight andbreast cancer recurrence and death: a report from theKorean breast cancer society. J. Clin. Oncol. 27, 5899-5905. https://doi.org/10.1200/JCO.2009.22.4436
  74. Nakashima, K., Narazaki, M. and Taga, T. (1997). Leptinreceptor (OB-R) oligomerizes with itself but not with itsclosely related cytokine signal transducer gp130. FEBS Lett.403, 79-82. https://doi.org/10.1016/S0014-5793(97)00013-6
  75. Neville, M. C., McFadden, T. B. and Forsyth, I. (2002).Hormonal regulation of mammary differentiation and milksecretion. J. Mammary. Gland Biol. Neoplasia. 7, 49-66. https://doi.org/10.1023/A:1015770423167
  76. Normanno, N., Bianco, C., Strizzi, L., Mancino, M., Maiello, M.R., De Luca, A., Caponigro, F. and Salomon, D. S. (2005).The ErbB receptors and their ligands in　cancer: Anoverview. Curr. Drug Targets 6, 243-257. https://doi.org/10.2174/1389450053765879
  77. Normanno, N., De Luca, A., Maiello, M. R., Campiglio, M.,Napolitano, M., Mancino, M., Carotenuto, A., Viglietto, G.and Menard, S. (2006a). The MEK/MAPK pathway isinvolved in the resistance of breast cancer cells to the EGFRtyrosine kinase inhibitor gefitinib. J. Cell Physiol. 207,420-427. https://doi.org/10.1002/jcp.20588
  78. Normanno, N., De Luca, A., Bianco, C., Strizzi, L., Mancino, M.,Maiello, M. R.,　Carotenuto, A., De Feo, G., Caponigro, T.and Salomons, D. S. (2006b). Epidermal　growth factorreceptor (EGFR) signaling in cancer. Gene 366, 2-16. https://doi.org/10.1016/j.gene.2005.10.018
  79. O’Brien, S. N., Welter, B. H. and Price, T. M. (1999). Presenceof leptin in breast cell lines and breast tumors. Biochem.Biophys. Res. Commun. 259, 695-698. https://doi.org/10.1006/bbrc.1999.0843
  80. Ogunwobi, O., Mutungi, G. and Beales, I. L. (2006). Leptinstimulates proliferation and inhibits apoptosis in Barrett’sesophageal adenocarcinoma cells by cyclooxygenase-2-dependent, prostaglandin-E2-mediated transactivation of theepidermal growth factor receptor and c-Jun NH2-terminalkinase activation. Endocrinology 147, 4505. https://doi.org/10.1210/en.2006-0224
  81. Okumura, M., Yamamoto, M., Sakuma, H., Kojima, T., Maruyama,T., Jamali, M., Cooper, D. R. and Yasuda, K. (2002). Leptinand high glucose stimulate cell proliferation in MCF-7 humanbreast cancer cells: Reciprocal involvement of PKC-alphaand PPAR expression. Biochim. Biophys. Acta. 1592,107-116. https://doi.org/10.1016/S0167-4889(02)00276-8
  82. Okuya, S., Tanabe, K., Tanizawa, Y. and Oka, Y. (2001). Leptinincreases the viability of isolated rat pancreatic islets bysuppressing apoptosis. Endocrinology 142, 4827-4830. https://doi.org/10.1210/en.142.11.4827
  83. Onuma, M., Bub, J. D., Rummel, T. L. and Iwamoto, Y. (2003).Prostate cancer cell-adipocyte interaction: Leptin mediatesandrogen-independent prostate cancer cell proliferationthrough c-Jun NH2-terminal kinase. J. Biol. Chem. 278,42660-42667. https://doi.org/10.1074/jbc.M304984200
  84. Park, H. Y., Kwon, H. M., Lim, H. J., Hong, B. K., Lee, J. Y.,Park, B. E., Jang, Y., Cho, S. Y. and Kim, H. S. (2001).Potential role of leptin in angiogenesis: Leptin induces endothelialcell proliferation and expression of matrix metalloproteinasesin vivo and in vitro. Exp. Mol. Med. 33, 95-102. https://doi.org/10.1038/emm.2001.17
  85. Petridou, E., Papadiamantis, Y., Markopoulos, C., Spanos, E.,Dessypris, N. and Trichopoulos, D. (2000). Leptin and insulingrowth factor I in relation to breast cancer (Greece). CancerCauses Control 11, 383-388. https://doi.org/10.1023/A:1008903727238
  86. Potter, J. D., Cerhan, J. R., Sellers, T. A., McGovern, P. G.,Drinkard, C., Kushi, L. R. and Folsom, A. R. (1995). Progesteroneand estrogen receptors and mammary neoplasia inthe Iowa Women’s Health Study: How many kinds of breastcancer are there? Cancer Epidemiol. Biomarkers Prev. 4,319-326.
  87. Rose, D. P., Gilhooly, E. M. and Nixon, D. W. (2002). Adverseeffects of obesity on breast cancer prognosis, and thebiological actions of leptin (review). Int. J. Oncol.　21, 1285-1292.
  88. Rose D. P., Komninou, D. and Stephenson, G. D. (2004).Obesity, adipocytokines, and insulin resistance in breastcancer. Obese. Rev. 5, 153-165. https://doi.org/10.1111/j.1467-789X.2004.00142.x
  89. Rouet-Benzineb, P., Aparicio, T., Guilmeau, S., Pouzet, C.,Descatoire, V., Buyse, M. and Bado, A. (2004). Leptin counteractssodium butyrate-induced apoptosis in human coloncancer HT-29 cells via NF-kappaB signaling. J. Biol. Chem.279, 16495-16502. https://doi.org/10.1074/jbc.M312999200
  90. Sato, H., Takino, T., Okada, Y., Cao, J., Shinagawa, A. andYamamoto, E. (1994). A matrix metalloproteinase expressedon the surface of invasive tumor cells. Nature 370, 61-65. https://doi.org/10.1038/370061a0
  91. Saxena, N. K., Taliaferro-Smith, L., Knight, B. B., Merlin, D.,Anania, F. A., O’Regan, R. M. and Sharma, D. (2008).Bidirectional crosstalk between leptin and insulin-like growthfactor-I signaling promotes invasion and migration of breastcancer cells via transactivation of epidermal growth factorreceptor. Cancer Res. 68, 9712-9722. https://doi.org/10.1158/0008-5472.CAN-08-1952
  92. Schwartz, M. W., Baskin, D. G., Kaiyala, K. J. and Woods, S. C.(1999). Model for the regulation of energy balance andadiposity by the central nervous system 1-3. Am. J. Clin.Nutr. 69, 584-596. https://doi.org/10.1093/ajcn/69.4.584
  93. Shida, D., Kitayama, J. and Mori, K. (2005). Transactivation ofepidermal growth factor receptor is involved in leptin-inducedactivation of janus-activated kinase 2 and extracellularsignal-regulated kinase 1/2 in human gastric cancer cells.Cancer Res. 65, 9159. https://doi.org/10.1158/0008-5472.CAN-05-0598
  94. Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., Garcia-Cardena, G., Papapetropoulos, A., Sessa, W. C., Madge, L.A., Schechner, J. S., Schwabb, M. B., Polverini, P. J. andFlores-Riveros, J. R. (1998). Biological action of leptin as anangiogenic factor. Science 281, 1683-1686. https://doi.org/10.1126/science.281.5383.1683
  95. Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A.and McGuire, W. L. (1987). Human breast cancer: correlationof relapse and survival with amplification of the HER-2/neuoncogene. Science 235, 235177-235182.
  96. Smith-Kirwin, S. M., O’Connor, D. M., De Johnston, J., Lancey,E. D., Hassink, S. G. and Funanage, V. L. (1998). Leptinexpression in human mammary epithelial cells and breastmilk. J. Clin. Endocrinol. Metab. 83, 1810-1813. https://doi.org/10.1210/jc.83.5.1810
  97. Soma, D., Kitayama, Joji., Yamashita, H., Miyato, H., Ishikawa,M. and Nagawa, H. (2008). Leptin augments proliferation ofbreast cancer cells via transactivation of HER2. J. Surg. Res.149, 9-14. https://doi.org/10.1016/j.jss.2007.10.012
  98. Somasundar, P., Yu, A. K., Vona-Davis, L. and McFadden, D.W. (2003). Differential effects of leptin on cancer in vitro. J.Surg. Res. 113, 50-55. https://doi.org/10.1016/S0022-4804(03)00166-5
  99. Somasundar, P., Frankenberry, K. A., Skinner, H., Vedula, G.,McFadden, D. W., Riggs, D., Jackson, B., Vangilder, R.,Hileman, S. M. and Vona-Davis, L. C. (2004). Prostatecancer cell proliferation is influenced by leptin. J. Surg. Res.118, 71-82. https://doi.org/10.1016/j.jss.2004.01.017
  100. Stahl, N., Farruggella, T. J., Boulton, T. G., Zhong, Z., Darnell,J. E. and Yancopoulos, G. D. (1995). Choice of STATs andother substrates specified by modular tyrosine based motifsin cytokine receptors. Science 267, 1349-1353. https://doi.org/10.1126/science.7871433
  101. Stattin, P., Soderberg, S., Hallmans, G., Bylund, A., Kaaks, R.,Stenman, U. H., Bergh, A. and Olsson, T. (2001). Leptin isassociated with increased prostate cancer risk: A nestedcase-referent study. J. Clin. Endocrinol. Metab. 86, 1341-1345. https://doi.org/10.1210/jc.86.3.1341
  102. Stephenson, G. D. and Rose, D. P. (2003). Breast cancer andobesity: An update. Nutr. Cancer 45, 1-16. https://doi.org/10.1207/S15327914NC4501_1
  103. Stetler-Stevenson, W. G. (1990). Type IV collagenase in tumorinvasion and metastasis.　Cancer Metastasis Rev. 9, 289-303. https://doi.org/10.1007/BF00049520
  104. Surmacz, E. (2007). Obesity hormone leptin: A new target inbreast cancer? Breast Cancer Res. 9, 301. https://doi.org/10.1186/bcr1638
  105. Sweeney, G. (2002). Leptin signaling. Cell Signal 14, 655-663. https://doi.org/10.1016/S0898-6568(02)00006-2
  106. Szanto, I. and Kahn, C. R. (2000). Selective interaction betweenleptin and insulin　signaling pathways in a hepatic cell line.Proc. Natl. Acad. Sci. USA. 97, 2355-2360. https://doi.org/10.1073/pnas.050580497
  107. Takeda, K., Naguchi, K, Shi, W., Tanaka, T., Matsumoto, M.,Yoshida, N., Kishimoto, T. and Akira, S. (1997). Targeteddisruption of the mouse Stat3 gene leads to early embryoniclethality. Proc. Natl. Acad. Sci. USA. 94, 3801-3804. https://doi.org/10.1073/pnas.94.8.3801
  108. Tartaglia, L. A., Dembski, M., Weng, X., Deng, N., Culpepper,J., Devos, R., Richards, G. J., Campfield, L. A., Clark, F. T.,Deeds, J., Muir, C., Sanker, S., Moriarty, A., Moore, K. J.,Smutko, J. S., Mays, G. G., Woolf, E. A., Monroe, C. A. andTepper, R. I. (1995). Identification and expression cloning ofa leptin receptor, OB-R. Cell 83, 1263-1271. https://doi.org/10.1016/0092-8674(95)90151-5
  109. Tartaglia, L. A. (1997). The leptin receptor. J. Biol. Chem. 272,6093-6096. https://doi.org/10.1074/jbc.272.10.6093
  110. Tessitore, L., Vizio, B., Jenkins, O., De Stefano, I., Ritossa, C.,Argiles, J. M., Benedetto, C. and Mussa, A. (2000). Leptinexpression in colorectal and breast cancer patients. Int. J.Mol. Med. 5, 421-426.
  111. Tryggvason, K., Hoyhtya, M. and Pyke, C. (1993). Type IVcollagenase in invasive tumors. Breast Cancer Res. Treat24, 209-218. https://doi.org/10.1007/BF01833261
  112. Tsuchiya, T., Shimizu, H., Horie, T. and Mori, M. (1999).Expression of leptin receptor in lung: Leptin as a growthfactor. Eur. J. Pharmacol. 365, 273-279. https://doi.org/10.1016/S0014-2999(98)00884-X
  113. Ura, H., Bonfil, R. D., Reich, R., Reddel, R., Pfeifer, A., Harris,C. C. and Klein-Sznto, A. J. (1989). Expression of type IVcollagenase and procollagen genes and its correlation withthe tumorigenic, invasive, and metastatic abilities of oncogenetransformedhuman bronchial epithelial cells. Cancer Res.49, 4615-4621.
  114. Vona-Davis, L. and Rose, D. P. (2007). Adipokines as endocrine,paracrine, and autocrine factors in breast cancer riskand progression. Endocr. Relat. Cancer 14, 189-206. https://doi.org/10.1677/ERC-06-0068
  115. White, D. W. and Tartaglia, L. A. (1996). Leptin and OB-R: Bodyweight regulation by a cytokine receptor. Cytokine GrowthFactor Rev. 7, 303-309. https://doi.org/10.1016/S1359-6101(96)00040-8
  116. White, D. W., Kuropatwinski, K. K., Devos, R., Baumann, H. andTartaglia, L. A. (1997). Leptin receptor (OB-R) signaling. J.Biol. Chem. 272, 4065-4071. https://doi.org/10.1074/jbc.272.7.4065
  117. White, D. W. and Tartaglia, L. A. (1999). Evidence for ligandindependenthomooligomerization of leptin receptor (OB-R)isoforms: A proposed mechanism permitting productivelong-form signaling in the presence of excess shortformexpression. J. Cell. Biochem. 73, 278-288. https://doi.org/10.1002/(SICI)1097-4644(19990501)73:2<278::AID-JCB13>3.0.CO;2-W
  118. Yarden, Y. (2001). Biology of HER2 and its importance in breastcancer. Oncology 61, 1-13.
  119. Yin, N., Wang, D., Zhang, H., Yi, X., Sun, X., Shi, B., Wu, H.,Wu, G., Wang, X. and Shang, Y. (2004). Molecular mechanismsinvolved in the growth stimulation of breast cancercells by leptin. Cancer Res. 64, 5870-5875. https://doi.org/10.1158/0008-5472.CAN-04-0655
  120. Zabeau, L., Lavens, D., Peelman, F., Eycherman, S., Vandekerckhove,J. and Tavernier, J. (2003). The ins and outs ofleptin receptor activation. FEBS Lett. 546, 45-50. https://doi.org/10.1016/S0014-5793(03)00440-X
  121. Zhang, H. H., Kumar, S., Barnett, A. H. and Eggo, M. C. (2000).Tumor necrosis factor-alpha exerts dual effects on humanadipose leptin synthesis and release. Mol. Cell. Endocrinol.159, 79-88. https://doi.org/10.1016/S0303-7207(99)00194-X
  122. Zhang, Y., Proenca, R., Maffei, M., Barone, M., Leopold, L. andFriedman, J. M. (1994). Positional cloning of the mouseobese gene and its human homologue. Nature 372, 425-432. https://doi.org/10.1038/372425a0
  123. Zhao, A. Z., Bornfeldt, K. E. and Beavo, J. A. (1998). Leptininhibits insulin secretion by activation of phosphodiesterase3B. J. Clin. Invest. 102, 869-873. https://doi.org/10.1172/JCI3920

Cited by

  1. Cross-regulation between protein L-isoaspartyl O-methyltransferase and ERK in epithelial mesenchymal transition of MDA-MB-231 cells vol.32, pp.9, 2010, https://doi.org/10.1038/aps.2011.94
  2. Serum and Tissue Expression Levels of Leptin and Leptin Receptor Are Putative Markers of Specific Feline Mammary Carcinoma Subtypes vol.8, pp.None, 2010, https://doi.org/10.3389/fvets.2021.625147