Browse > Article
http://dx.doi.org/10.5487/TR.2011.27.4.253

Cell Growth of BG-1 Ovarian Cancer Cells was Promoted by 4-Tert-octylphenol and 4-Nonylphenol via Downregulation of TGF-β Receptor 2 and Upregulation of c-myc  

Park, Min-Ah (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Hwang, Kyung-A (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Lee, Hye-Rim (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Yi, Bo-Rim (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Choi, Kyung-Chul (Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University)
Publication Information
Toxicological Research / v.27, no.4, 2011 , pp. 253-259 More about this Journal
Abstract
Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.
Keywords
Endocrine disrupting chemicals; Estrogen; OP; NP; TGF-${\beta}1$; c-myc; Ovarian cancer cells;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Yilmaz, M., Maass, D., Tiwari, N., Waldmeier, L., Schmidt, P., Lehembre, F. and Christofori, G. (2011). Transcription factor Dlx2 protects from TGFbeta-induced cell-cycle arrest and apoptosis. EMBO. J., 30, 4489-4499.   DOI   ScienceOn
2 Regan, M.M., Viale, G., Mastropasqua, M.G., Maiorano, E., Golouh, R., Carbone, A., Brown, B., Suurkula, M., Langman, G., Mazzucchelli, L., Braye, S., Grigolato, P., Gelber, R.D., Castiglione- Gertsch, M., Price, K.N., Coates, A.S., Goldhirsch, A. and Gusterson, B. (2006). Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J. Natl. Cancer Inst., 98, 1571-1581.   DOI   ScienceOn
3 Schuster, N. and Krieglstein, K. (2002). Mechanisms of TGF-betamediated apoptosis. Cell Tissue Res., 307, 1-14.   DOI
4 Shanle, E.K. and Xu, W. (2011). Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem. Res. Toxicol., 24, 6-19.   DOI   ScienceOn
5 Terasaka, S., Inoue, A., Tanji, M. and Kiyama, R. (2006). Expression profiling of estrogen-responsive genes in breast cancer cells treated with alkylphenols, chlorinated phenols, parabens, or bis- and benzoylphenols for evaluation of estrogenic activity. Toxicol. Lett., 163, 130-141.   DOI   ScienceOn
6 Theriault, B.L. and Nachtigal, M.W. (2011). Human ovarian cancer cell morphology, motility, and proliferation are differentially influenced by autocrine TGFbeta superfamily signalling. Cancer Lett., 313, 108-121.   DOI   ScienceOn
7 Watanabe, J., Kamata, Y., Seo, N., Okayasu, I. and Kuramoto, H. (2007). Stimulatory effect of estrogen on the growth of endometrial cancer cells is regulated by cell-cycle regulators. J. Steroid. Biochem. Mol. Biol., 107, 163-171.   DOI   ScienceOn
8 Yi, B.R., Kang, N.H., Hwang, K.A., Kim, S.U., Jung, E.B. and Choi, K.C. (2011). Antitumor Therapeuic Effects of Cytosinf Deaminase and Interferon-â Against Endometrial Cancer Cells Using Genetically Ebngineered Stem Cells In Vitro. Anticancer Reserch, 31, 2853-2861.
9 McCaffrey, T.A., Consigli, S., Du, B., Falcone, D.J., Sanborn, T.A., Spokojny, A.M. and Bush, H.L., Jr. (1995). Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions. Conversion from an antiproliferative to profibrotic response to TGF-beta1. J. Clin. Invest., 96, 2667-2675.   DOI   ScienceOn
10 Nilsson, E.E. and Skinner, M.K. (2002). Role of transforming growth factor beta in ovarian surface epithelium biology and ovarian cancer. Reprod. Biomed. Online, 5, 254-258.   DOI   ScienceOn
11 Pedram, A., Razandi, M. and Levin, E.R. (2006). Nature of functional estrogen receptors at the plasma membrane. Mol. Endocrinol., 20, 1996-2009.   DOI   ScienceOn
12 Osada, H., Yoshitake, Y., Ikeda, T., Ishigaki, Y., Takata, T., Tomosugi, N., Sasaki, H. and Yonekura, H. (2011). Ultraviolet Binduced expression of amphiregulin and growth differentiation factor 15 in human lens epithelial cells. Mol. Vis., 17, 159-169.
13 Park, M.A., Hwang, K.A., Lee, H.R., Yi, B.R., Jeung, E.B. and Choi, K.C. (2011). Cell growth of BG-1 ovarian cancer cells was promoted by di-n-butyl phthalate and hexaboromocyclododecane via upregulation of cyclin D and cell cycle-dependent kinase-4 genes. Mol. Med. Report. In press.
14 Park, S.H., Kim, K.Y., An, B.S., Choi, J.H., Jeung, E.B., Leung, P.C. and Choi, K.C. (2009). Cell growth of ovarian cancer cells is stimulated by xenoestrogens through an estrogen-dependent pathway, but their stimulation of cell growth appears not to be involved in the activation of the mitogen-activated protein kinases ERK-1 and p38. J. Reprod. Dev., 55, 23-29.   DOI   ScienceOn
15 Hwang, K.A., Park, S.H., Yi, B.R. and Choi, K.C. (2011). Gene alterations of ovarian cancer cells expressing estrogen receptors by estrogen and bisphenol a using microarray analysis. Lab. Anim. Res., 27, 99-107.   DOI
16 Ito, I., Hanyu, A., Wayama, M., Goto, N., Katsuno, Y., Kawasaki, S., Nakajima, Y., Kajiro, M., Komatsu, Y., Fujimura, A., Hirota, R., Murayama, A., Kimura, K., Imamura, T. and Yanagisawa, J. (2010). Estrogen inhibits transforming growth factor beta signaling by promoting Smad2/3 degradation. J. Biol. Chem., 285, 14747-14755.   DOI   ScienceOn
17 Khan, S.A., Rogers, M.A., Khurana, K.K., Meguid, M.M. and Numann, P.J. (1998). Estrogen receptor expression in benign breast epithelium and breast cancer risk. J. Natl. Cancer Inst., 90, 37-42.   DOI   ScienceOn
18 Massague, J., Seoane, J. and Wotton, D. (2005). Smad transcription factors. Genes. Dev., 19, 2783-2810.   DOI   ScienceOn
19 Kim, D.Y., Kim, M.J., Kim, H.B., Lee, J.W., Bae, J.H., Kim, D.W., Kang, C.D. and Kim, S.H. (2011). Suppression of multidrug resistance by treatment with TRAIL in human ovarian and breast cancer cells with high level of c-Myc. Biochim. Biophys. Acta., 1812, 796-805.   DOI   ScienceOn
20 Kochukov, M.Y., Jeng, Y.J. and Watson, C.S. (2009). Alkylphenol xenoestrogens with varying carbon chain lengths differentially and potently activate signaling and functional responses in GH3/B6/F10 somatomammotropes. Environ Health Perspect., 117, 723-730.   DOI   ScienceOn
21 Massague, J. (2008). TGFbeta in Cancer. Cell, 134, 215-230.   DOI   ScienceOn
22 Matsuda, T., Yamamoto, T., Muraguchi, A. and Saatcioglu, F. (2001). Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3. J. Biol. Chem., 276, 42908-42914.   DOI   ScienceOn
23 Dunfield, L.D. and Nachtigal, M.W. (2003). Inhibition of the antiproliferative effect of TGFbeta by EGF in primary human ovarian cancer cells. Oncogene, 22, 4745-4751.   DOI   ScienceOn
24 Elliott, R.L. and Blobe, G.C. (2005). Role of transforming growth factor Beta in human cancer. J. Clin. Oncol., 23, 2078-2093.   DOI   ScienceOn
25 Feng, X.H. and Derynck, R. (2005). Specificity and versatility in tgf-beta signaling through Smads. Annu. Rev. Cell Dev. Biol., 21, 659-693.   DOI   ScienceOn
26 Hagiwara, H., Sugizaki, T., Tsukamoto, Y., Senoh, E., Goto, T. and Ishihara, Y. (2008). Effects of alkylphenols on bone metabolism in vivo and in vitro. Toxicol. Lett., 181, 13-18.   DOI   ScienceOn
27 Gantus, M.A., Alves, L.M., Stipursky, J., Souza, E.C., Teodoro, A.J., Alves, T.R., Carvalho, D.P., Martinez, A.M., Gomes, F.C. and Nasciutti, L.E. (2011). Estradiol modulates TGF-beta1 expression and its signaling pathway in thyroid stromal cells. Mol. Cell Endocrinol., 337, 71-79.   DOI   ScienceOn
28 Gomis, R.R., Alarcon, C., Nadal, C., Van Poznak, C. and Massague, J. (2006). C/EBPbeta at the core of the TGFbeta cytostatic response and its evasion in metastatic breast cancer cells. Cancer Cell, 10, 203-214.   DOI   ScienceOn
29 Goto, N., Hiyoshi, H., Ito, I., Tsuchiya, M., Nakajima, Y. and Yanagisawa, J. (2011). Estrogen and antiestrogens alter breast cancer invasiveness by modulating the transforming growth factor-beta signaling pathway. Cancer Sci., 102, 1501-1508.   DOI   ScienceOn
30 Hill, J.J., Tremblay, T.L., Cantin, C., O'Connor-McCourt, M., Kelly, J.F. and Lenferink, A.E. (2009). Glycoproteomic analysis of two mouse mammary cell lines during transforming growth factor (TGF)-beta induced epithelial to mesenchymal transition. Proteome. Sci., 7, 2.   DOI   ScienceOn
31 Asimakopoulos, A.G., Thomaidis, N.S. and Koupparis, M.A. (2011). Recent trends in biomonitoring of bisphenol A, 4-toctylphenol, and 4-nonylphenol. Toxicol. Lett. In press.
32 Choi, S.M., Yoo, S.D. and Lee, B.M. (2004). Toxicological characteristics of endocrine-disrupting chemicals: developmental toxicity, carcinogenicity, and mutagenicity. J. Toxicol. Environ. Health B Crit. Rev., 7, 1-24.   DOI
33 Band, A.M. and Laiho, M. (2011). Crosstalk of TGF-beta and estrogen receptor signaling in breast cancer. J. Mammary Gland Biol. Neoplasia, 16, 109-115.   DOI
34 Chen, C.R., Kang, Y., Siegel, P.M. and Massague, J. (2002). E2F4/5 and p107 as Smad cofactors linking the TGFbeta receptor to c-myc repression. Cell, 110, 19-32.   DOI   ScienceOn
35 Choi, K.C. and Jeung, E.B. (2003). The biomarker and endocrine disruptors in mammals. J. Reprod. Dev., 49, 337-345.   DOI   ScienceOn
36 Diamanti-Kandarakis, E., Bourguignon, J.P., Giudice, L.C., Hauser, R., Prins, G.S., Soto, A.M., Zoeller, R.T. and Gore, A.C. (2009). Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev., 30, 293-342.   DOI   ScienceOn
37 Doisneau-Sixou, S.F., Sergio, C.M., Carroll, J.S., Hui, R., Musgrove, E.A. and Sutherland, R.L. (2003). Estrogen and antiestrogen regulation of cell cycle progression in breast cancer cells. Endocr. Relat. Cancer, 10, 179-186.   DOI