Kajian Peran Gen P53 dalam Tumorigenesis

Main Article Content

Retina Yunani

Abstract

Gene p53 is a tumor suppressor gene that in normal conditions is in ' standby ' mode , several studies show that pivotal point that lead to stimulation of p53 is DNA damage , heat shock , hypoxia, exposure of nitric oxide ( NO ) , the expression of oncogenes and some p53 pathways activation. p53 mechanism as a guardian of genome stability are cell cycle arrest, repair of DNA damaged, induce apoptosis, prevents angiogenesis , invasion and metastasis ability of the tumor. On many tumor , p53 is not loss , but mutated , the p53 mutant was expressed 70 % in lung cancer , and in different frequencies in other cancers . Then the role of p53 as a transcription factor that works to regulate genes involved in tumor suppression is indispensable .

Keywords:
Gene p53, Nitric oxide, DNA
References
Barboza, J.A., Liu, G., El-Naggar, A.K., and Lozano, G. 2006. p21 delays tumor onset by preservation of chromosomal stability. Proc. Natl. Acad. Sci. USA 103, 19842–19847.

Bai, L and W.G. Zhu.2006. p53: Structure, Function and Therapeutic Apllications. Journal of Cancer Molecules 2(4): 141-153

Bode AM, Dong Z. 2004.Post-translational modification of p53 intumorigenesis. Nat Rev Cancer 4: 793-805.

Chander H, Halpern M, Resnick-Silverman L, Manfredi JJ, Germain D. 2011.Skp2B overexpression alters a prohibitin-p53 axis and the transcription of PAPP-A,the protease of insulin-like growth factor binding protein 4. PLoS One;6:e22456.

Chen X, Ko LJ, Jayaraman L, Prives C. 1996.p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10: 2438-2451.

Derksen, P.W., X. Liu, F. Saridin, H. van der Gulden, J. Zevenhoven, B. Evers, J.R. van Beijnum, A.W. Griffioen, J. Vink, P. Krimpenfortl. 2006. Somatic inactivation of E­cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell. 10:437–449. doi:10.1016/j.ccr.2006.09.013

Dhar, G., S. Banerjee, K. Dhar, O. Tawfik, M.S. Mayo, P.J. Vanveldhuizen, and S.K. Banerjee. 2008. Gain of oncogenic function of p53 mutants induces invasive phenotypes in human breast cancer cells by silencing CCN5/WISP­2. Cancer Res. 68:4580–4587. doi:10.1158/0008­5472.CAN­ 08­0316

Fields S, Jang SK.1990. Presence of a potent transcription activating sequence in the p53 protein. Science 249: 1046-1049.

Gasco M, S. Shami and T. Crook. 2002.The p53 pathway in breast cancer. Breast cancer research. Vol 44 No.2

Garrison, S.P., Jeffers, J.R., Yang, C., Nilsson, J.A., Hall, M.A., Rehg, J.E., Yue, W., Yu, J.,Zhang, L., Onciu, M.,. 2008. Selection against PUMA gene expression in Myc-driven B cell lymphomagenesis. Mol. Cell. Biol. 28, 5391–5402.

George, P.2011.p53 How crucialis its role in cancer. International Journal of Current Pharmaceutical Research. Vol.3 Issue. 2

Hamano Y, Zeisberg M, Sugimoto H, Lively JC, Maeshima Y, Yang C. 2003.Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. Cancer Cell;3:589-601.

Hollstein M, Sidransky D, Vogelstein B, Harris CC.1991. p53 mutations in human cancers. Science 253: 49-53.

Isobe M, Emanuel BS, Givol D, Oren M, Croce CM.1986. Localizationof gene for human p53 tumour antigen to band 17p13. Nature320: 84-85.

Kogan­Sakin, I., Y. Tabach, Y. Buganim, A. Molchadsky, H. Solomon, S. Madar, I. Kamer, P. Stambolsky, A. Shelly, N. Goldfinger, et al. 2010. Mutant p53(R175H) upregulates Twist1 expression and promotes epithelial­ mesenchymal transition in immortalized prostate cells. Cell Death Differ. In press.

Kuerbitz, S.J., B.S. Plunkett, W.V. Walsh, M.B. Kastan. 1992. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc. Natl. Acad. Sci. USA 89: 7491–7495.

Muller, P.A.J., K.H. Vousden., J.C. Norman.2011. p53 and its mutants in tumor cell migration and invasion. J Cell Biol. Vol 192 No.2: 209-218

Lin J, Chen J, Elenbaas B, Levine AJ.1994. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus
5 E1B 55-kD protein. Genes Dev 8: 1235-1246.

Oren, M., and V. Rotter. 2010. Mutant p53 gain­of­function in cancer. Cold Spring Harb. Perspect. Biol. 2:a001107. doi:10.1101/cshperspect.a001107

Sakamuro D, Sabbatini P, White E, Prendergast GC. 1997.The polyproline region of p53 is required to activate apoptosis but not growth arrest. Oncogene 15: 887-898.

Sherr CJ. 1998.Tumor surveillance via the ARF-p53 pathway. Genes Dev 12: 2984-299.

Shiota, M., H. Izumi, T. Onitsuka, N. Miyamoto, E. Kashiwagi, A. Kidani, G. Hirano, M. Takahashi, S. Naito, and K. Kohno. 2008. Twist and p53 reciprocally regulate target genes via direct interaction. Oncogene. 27:5543–5553. doi:10.1038/onc.2008.176

Slee EA, O'Connor DJ, Lu X.2004. To die or not to die: how does p53decide? Oncogene 23: 2809-2818.

Teodoro JG, Parker AE, Zhu X, Green MR. 2006. p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase. Science;313:968-71.

Teodoro JG, Evans SK, Green MR.2007. Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome. J Mol Med.

Toledo, F., Krummel, K.A., Lee, C.J., Liu, C.W., Rodewald, L.W., Tang, M., and Wahl, G.M. 2006. A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network. Cancer Cell 9, 273–285.

Vogelstein B, Lane D, Levine AJ. 2000.Surfing the p53 network. Nature 408: 307-310.

Vousden KH, Lu X.2002. Live or let die: the cell's response to p53. Nat Rev Cancer 2: 594-604.

Wang, S.P., W.L. Wang, Y.L. Chang, C.T. Wu, Y.C. Chao, S.H. Kao, A. Yuan, C.W. Lin, S.C. Yang, W.K. Chan. 2009. p53 controls cancer cell invasion by inducing the MDM2­mediated degradation of Slug. Nat. Cell Biol. 11:694–704. doi:10.1038/ncb1875

Xue, W., Zender, L., Miething, C., Dickins, R.A., Hernando, E., KrizhanovskyV., Cordon-Cardo, C., and Lowe, S.W. 2007. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656–660.

Article Details

Author Biography

Retina Yunani, Fakultas Kedokteran Hewan Universitas Wijaya Kusuma Surabaya

Laboratorium Farmakologi dan Farmasi, Fakultas Kedokteran Hewan
Universitas Wijaya Kusuma Surabaya
Email: retina_yunani@yahoo.com