p16INK4a hypermethylation and p53, p16 and MDM2 protein expression in Esophageal Squamous Cell Carcinoma

BMC Cancer

Research Article

Bahram Memar¹  Hooman Khademi²  Masoud Sotoudeh²  Reza Malekzadeh²  Omeed Moaven³  Azadeh A'rabi³  Mohammad Reza Abbaszadegan³  Firouzeh Biramijamal⁴  Noushin Taghavi⁵ 

[1] Department of Pathology, Omid Hospital, MUMS, Mashhad, Iran;Digestive Disease Research Center (DDRC), Tehran University of Medical Sciences, Tehran, Iran;Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran;National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran;National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran;Digestive Disease Research Center (DDRC), Tehran University of Medical Sciences, Tehran, Iran;

关键词: Esophageal Squamous Cell Carcinoma;    Esophageal Squamous Cell Carcinoma Patient;    Golestan Province;    Esophageal Squamous Cell Carcinoma Tumor;    Normal Esophageal Tissue;   

DOI  :  10.1186/1471-2407-10-138

 received in 2009-11-16, accepted in 2010-04-13,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTumor suppressor genes p53 and p16INK4a and 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.MethodsCancerous 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.ResultsAbnormal 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).Conclusionsp16 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.

【 授权许可】

Unknown   
© Taghavi et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.