Abstract
p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type p53 or the functional activation of mutant-type p53 might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcriptionpolymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150 with wild-type p53, p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the p53 genotype.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Parkin D M, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin, 2005, 55(2): 74–108
Ke L. Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970–90. Int J Cancer, 2002, 102(3): 271–274
Lerut T, Coosemans W, De Leyn P, Van Raemdonck D, Deneffe G, Decker G. Treatment of esophageal carcinoma. Chest, 1999, 116(6 Suppl): 463S–465S
Zhan Q, Carrier F, Fornace A J Jr. Induction of cellular p53 activity by DNA-damaging agents and growth arrest. Mol Cell Biol, 1993, 13(7): 4242–4250
Hainaut P, Hernandez T, Robinson A, Rodriguez-Tome P, Flores T, Hollstein M, Harris C C, Montesano R. IARC Database of p53 gene mutations in human tumors and cell lines: updated compilation, revised formats and new visualisation tools. Nucleic Acids Res, 1998, 26(1): 205–213
May P, May E. Twenty years of p53 research: structural and functional aspects of the p53 protein. Oncogene, 1999, 18(53): 7621–7636
Zhan Q, Fan S, Bae I, Guillouf C, Liebermann D A, O’Connor P M, Fornace A J Jr. Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene, 1994, 9(12): 3743–3751
Greenblatt MS, Bennett WP, Hollstein M, Harris C C. Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res, 1994, 54(18): 4855–4878
Tanaka H, Shibagaki I, Shimada Y, Wagata T, Imamura M, Ishizaki K. Characterization of p53 gene mutations in esophageal squamous cell carcinoma cell lines: increased frequency and different spectrum of mutations from primary tumors. Int J Cancer, 1996, 65(3): 372–376
Ko L J, Prives C. p53: puzzle and paradigm. Genes Dev, 1996, 10(9): 1054–1072
Merchant A K, Loney T L, Maybaum J. Expression of wild-type p53 stimulates an increase in both Bax and Bcl-xL protein content in HT29 cells. Oncogene, 1996, 13(12): 2631–2637
Miyashita T, Krajewski S, Krajewska M, Wang H G, Lin H K, Liebermann D A, Hoffman B, Reed J C. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene, 1994, 9(6): 1799–1805
Pietenpol J A, Tokino T, Thiagalingam S, el-Deiry W S, Kinzler K W, Vogelstein B. Sequence-specific transcriptional activation is essential for growth suppression by p53. Proc Natl Acad Sci U S A, 1994, 91(6): 1998–2002
Moll U M, LaQuaglia M, Bénard J, Riou G. Wild-type p53 protein undergoes cytoplasmic sequestration in undifferentiated neuroblastomas but not in differentiated tumors. Proc Natl Acad Sci U S A, 1995, 92(10): 4407–4411
Moll U M, Ostermeyer A G, Haladay R, Winkfield B, Frazier M, Zambetti G. Cytoplasmic sequestration of wild-type p53 protein impairs the G1 checkpoint after DNA damage. Mol Cell Biol, 1996, 16(3): 1126–1137
Fan W, Jin S, Tong T, Zhao H, Fan F, Antinore M J, Rajasekaran B, Wu M, Zhan Q. BRCA1 regulates GADD45 through its interactions with the OCT-1 and CAAT motifs. J Biol Chem, 2002, 277(10): 8061–8067
Barnas C, Martel-Planche G, Furukawa Y, Hollstein M, Montesano R, Hainaut P. Inactivation of the p53 protein in cell lines derived from human esophageal cancers. Int J Cancer, 1997, 71(1): 79–87
Fujii T, Kato S, Yamana H, Tanaka Y, Fujita H, Shirouzu K, Morimatsu M. Expression of G1 cell cycle markers and the effect of adenovirus-mediated overexpression of p21Waf-1 in squamous cell carcinoma of the esophagus. Int J Oncol, 2001, 18(1): 157–163
Rigberg D A, Centeno J, Kim F S, Ke B, Swenson K, Maggard M, McFadden D W. Irradiation-induced up-regulation of Fas in esophageal squamous cell carcinoma is not accompanied by Fas ligand-mediated apoptosis. J Surg Oncol, 1999, 71(2): 91–96
el-Deiry W S. Regulation of p53 downstream genes. Semin Cancer Biol, 1998, 8(5): 345–357
Leng R P, Lin Y, Ma W, Wu H, Lemmers B, Chung S, Parant J M, Lozano G, Hakem R, Benchimol S. Pirh2, a p53-induced ubiquitinprotein ligase, promotes p53 degradation. Cell, 2003, 112(6): 779–791
Zhan Q. Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage. Mutat Res, 2005, 569(1–2): 133–143
Rigberg D A, Kim F S, Blinman T A, Cole M A, Lane J S, So J, McFadden D W. p21 expression is increased by irradiation in esophageal squamous cell carcinoma. J Surg Res, 1998, 76(2): 137–142
el-Deiry W S, Kern S E, Pietenpol J A, Kinzler K W, Vogelstein B. Definition of a consensus binding site for p53. Nat Genet, 1992, 1(1): 45–49
Hollstein M, Sidransky D, Vogelstein B, Harris C C. p53 mutations in human cancers. Science, 1991, 253(5015): 49–53
Liang S H, Clarke M F. Regulation of p53 localization. Eur J Biochem, 2001, 268(10): 2779–2783
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ji, J., Wu, K., Wu, M. et al. p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines. Front. Med. China 4, 412–418 (2010). https://doi.org/10.1007/s11684-010-0260-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11684-010-0260-x