Inducing apoptosis by the inhibition of c-myb in oral squamous carcinoma cell line, KB cell

  • Lee, Jung-Chang (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Moon, Hyun-Ju (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Lee, Young-Hee (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Jung, Ji-Eun (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Sharma, Manju (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Jhee, Eun-Jung (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University) ;
  • Yi, Ho-Keun (Department of Oral biochemistry, School of Dentistry and Institute of Oral-bioScience, Chonbuk National University)
  • Published : 2007.12.31

Abstract

Oral squamous cell carcinoma (OSCC) is the most common malignancy and is a major cause of worldwide cancer mortality. The proto-oncogene c-myb plays an important role in regulation of cell growth and differentiation, and it is expressed at high levels in hematopoietic cells and many other types of cancers. However, the function of c-myb is not well known in OSCC. The present study aimed to reveal the function of c-myb and to test the alternation of cell growth and signaling by c-myb in OSCC. In this study, c-myb and dominant-negatibe myb(DNmyb) were expressed in an adenovirus-mediated gene delivery system to KB cells. The over-expressed c-myb brought increased cellular proliferation compared with control cells. However, DN-myb infected KB cells showed significant reduction of cell growth and enhanced induction of apoptosis to activate PARP and caspase 9. c-myb induced increase of IGF-I, -II and IGF-IR expressions while DN-myb down-regulated these expression. Activation of ERK and Akt/PKB pathway was shown only in c-myb transduced cells. These findings suggest that the role of c-myb in cell growth of oral cancer cells is partially mediated through the modulation of IGFs, ERK and Akt/PKB. From this results, DN-myb is strongly recommended as a curable gene for the treatment of c-myb dependent malignancies such as OSCC.

Keywords

References

  1. Daftary, D. K., Murti, P. R., Bhonsle, R. B., Gupta, P. C., Mehta, F. S. and Pindborg, J. J.: Risk factors and risk markers for oral cancer in high incidence areas of the world. In Oral Cancer, vol. 2, edited by Jhonson, N. W., pp 29-63, Cambridge University Press, Cambridge, 1991
  2. Datta, K., Franke, T. F., Chan, T. O., Makris, A., Yang, S. I., Kaplan, D. R., Morrison, D. K., Golemis, E. A. and Tsichlis, P. N.: AH/PH domain-mediated interaction between Akt molecules and its potential role in Akt regulation. Mol. Cell Biol. 15:2304-2310, 1995 https://doi.org/10.1128/MCB.15.4.2304
  3. Guerin, M., Sheng, Z. M., Andrieu, N. and Riou, G.: Strong association between c-myb and estrogen-receptor expression in human breast cancer. Oncogene. 5: 131-135, 1990
  4. Howe, K. M., Reakes, C. F. and Watson, R. J.: Characterization of the sequence-specific interaction of mouse c-myb protein with DNA. EMBO J. 9:161-169, 1990
  5. Ibanez, C. E. and Lipsick, J. S.: Trans activation of gene expression by v-myb. Mol. Cell. Biol. 10:2285-2293, 1990 https://doi.org/10.1128/MCB.10.5.2285
  6. Introna, M., Luchetti, M., Castellano, M., Arsura, M. and Golay, J.: The myb oncogene family of transcription factors: potent regulators of hematopoietic cell proliferation and differentiation. Semin. Cancer Biol. 5: 113-124, 1994
  7. Luscher, B. and Eisenman, RN.: New light on Myc and Myb. Genes Dev. 4:2235-2241, 1990 https://doi.org/10.1101/gad.4.12b.2235
  8. Melotti, P., Ku, DH. and Calabretta, B.: Regulation of the expression of the hematopoietic stem cell antigen CD34: role of c-myb. J. Exp. Med. 179:1023-1028, 1994 https://doi.org/10.1084/jem.179.3.1023
  9. Nishina, Y., Nakagoshi, H., Imamoto, F., Gonda, T. J. and Ishii, S.: Trans-activation by the c-myb proto-oncogene. Nucleic Acids Res. 17:107-117, 1989 https://doi.org/10.1093/nar/17.1.107
  10. Rane, S. G. and Reddy E. P.: JAKs, STATs and Src kinases in hematopoiesis. Oncogene. 21:3334-3358, 2002 https://doi.org/10.1038/sj.onc.1205398
  11. Ratajczak, M. Z., Kant, J. A., Luger, S. M., Hijiya, N., Zhang, J., Zon, G. and Gewirtz, A. M.: In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. Proc. Natl. Acad. Sci. USA 89: 11823-11827, 1992
  12. Reiss, K., Ferber, A., Travali, S., Porcu, P., Phillips, P. D. and Baserga, R.: The protooncogene c-myb increases the expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor messenger RNAs by a transcriptional mechanism. Cancer Res. 51:5997-6000, 1991
  13. Sakura, H., Kanei-Ishii, C., Nagase, T., Nakagoshi, H., Gonda, T. J. and Ishii, S.: Delineation of three functional domains of the transcriptional activator encoded by the c-myb protooncogene. Proc. Natl. Acad. Sci. USA 86:5758-5762, 1989
  14. Sala, A.: B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer. Eur. J. Cancer. 41:2479-2484, 2005 https://doi.org/10.1016/j.ejca.2005.08.004
  15. Saranath, D.: Integrated biology and molecular pathology of oral cancer. In Contemporary issues in oral cancer, edited by Saranath, D., pp 30-71, Oxford University Press, New Delhi, 2000
  16. Scharf, J.G. and Braulke, T.: The role of the IGF axis in hepatocarcinogenesis. Horm. Metab. Res. 35:685-693, 2003 https://doi.org/10.1055/s-2004-814151
  17. Sitzmann, J., Noben-Trauth, K. and Klempnauer, KH.: Expression of mouse c-myb during embryonic development. Oncogene. 11:2273-2279, 1995
  18. Suzuki, K. and Takahashi, K.: Anchorage-independent activation of mitogen-activated protein kinase through phosphatidy-linositol-3 kinase by insulin-like growth factor I. Biochem. Biophys. Res. Commun. 272:111-115, 2000 https://doi.org/10.1006/bbrc.2000.2737
  19. Thompson, MA. and Ramsay, R.G.:Myb: an old oncoprotein with new roles. Bioessays. 17:341-350, 1995 https://doi.org/10.1002/bies.950170410
  20. Torelli, G., Venturelli, D., Colo, A., Zanni, C., Selleri, L., Moretti, L., Calabretta, B. and Torelli, U.: Expression of cmyb protooncogene and other cell cycle-related genes in normal and neoplastic human colonic mucosa. Cancer Res. 47:5266-5269, 1987
  21. Yi, HK., Nam, SY., Kim, JC., Kim, JS., Lee, DY. and Hwang, PH.: Induction of apoptosis in K562 cells by dominant negative c-myb. Exp. Hematol. 30:1139-1146, 2002 https://doi.org/10.1016/S0301-472X(02)00896-2