P16INK4ahypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

Taghavi, N. and Biramijamal, F. and Sotoudeh, M. and Khademi, H. and Malekzadeh, R. and Moaven, O. and Memar, B. and A'Rabi, A. and Abbaszadegan, M. R. (2010) P16INK4ahypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma. BMC Cancer, 10.

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Abstract

Background: Tumor suppressor genes p53 and p16INK4aand the proto-oncogene MDM2 are considered to be essential G1 cell cycle regulatory genes whose loss of function is associated with ESCC carcinogenesis. We assessed the aberrant methylation of the p16 gene and its impact on p16INK4aprotein expression and correlations with p53 and MDM2 protein expressions in patients with ESCC in the Golestan province of northeastern Iran in which ESCC has the highest incidence of cancer, well above the world average.Methods: Cancerous tissues and the adjacent normal tissue obtained from 50 ESCC patients were assessed with Methylation-Specific-PCR to examine the methylation status of p16. The expression of p16, p53 and MDM2 proteins was detected by immunohistochemical staining.Results: Abnormal expression of p16 and p53, but not MDM2, was significantly higher in the tumoral tissue. p53 was concomitantly accumulated in ESCC tumor along with MDM2 overexpression and p16 negative expression. Aberrant methylation of the p16INK4agene was detected in 31/50 (62) of esophageal tumor samples, while two of the adjacent normal mucosa were methylated (P < 0.001). p16INK4aaberrant methylation was significantly associated with decreased p16 protein expression (P = 0.033), as well as the overexpression of p53 (P = 0.020).Conclusions: p16 hypermethylation is the principal mechanism of p16 protein underexpression and plays an important role in ESCC development. It is associated with p53 protein overexpression and may influence the accumulation of abnormally expressed proteins in p53-MDM2 and p16-Rb pathways, suggesting a possible cross-talk of the involved pathways in ESCC development. © 2010 Taghavi et al; licensee BioMed Central Ltd.

Item Type: Article
Additional Information: Cited By :55 Export Date: 16 February 2020 CODEN: BCMAC Correspondence Address: Abbaszadegan, M.R.; Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran; email: abbaszadeganmr@mums.ac.ir
Uncontrolled Keywords: bisulfite cyclin dependent kinase inhibitor 2A protein MDM2 protein p16 protein p53 MDM2 protein, human TP53 protein, human tumor marker adult aged article cancer survival clinical article controlled study DNA methylation esophageal squamous cell carcinoma female histopathology human human cell human tissue immunohistochemistry immunoreactivity Iran male molecular interaction polymerase chain reaction protein expression protein function survival time tumor localization tumor volume chemistry chi square distribution CpG island esophagus tumor gene expression regulation genetics Kaplan Meier method middle aged mortality pathology squamous cell carcinoma Aged, 80 and over Carcinoma, Squamous Cell Chi-Square Distribution CpG Islands Cyclin-Dependent Kinase Inhibitor p16 Esophageal Neoplasms Gene Expression Regulation, Neoplastic Humans Kaplan-Meiers Estimate Proto-Oncogene Proteins c-mdm2 Tumor Markers, Biological Tumor Suppressor Protein p53
Subjects: WI Digestive System
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib7 lib7
Date Deposited: 02 May 2020 03:50
Last Modified: 02 May 2020 03:50
URI: http://eprints.mums.ac.ir/id/eprint/17130

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