The Methylation of p16 Gene Promoter in Carcinogenesis and Development of Breast Cancer

ZHANG Yi-bing, LU He-xiang, ZHANG Xin-ran. et al

Abstract

To investigate the protein expression of the p16 gene and the methylation of its promoter in breast cancer, and to analyze the correlation between the p16 DNA methylation and the clinicopathological features. Methods Immuno-histochemistry technique (SP method) and methylation-specific-PCR (MSP) were used to detect p16 protein expression and the methylation of the p16 promoter in 47 breast cancer samples as well as in 20 hyperplasia samples of mammary glands. Results The p16 protein expression in breast cancer samples significantly lower when compared with those of hyperplasia samples (48.9% vs. 70.0%) and p16 methylation was more frequent in breast-tumor tissues when compared with those of hyperplasia samples (38.3% vs. 20.0%), but the statistical significance wasn’t found (P>0.05). Down-regulation of p16 protein was negatively correlation with p16 gene hypermethylation (r=-0.33, P=0.02). Meanwhile, p16 methylation in breast cancer tissues correlated with histological type, lymph node metastasis, but not correlated with the age, tumor diameter, TNM stage, expression of estrogen receptor (ER) and progesterone receptor (PR) gene status. Conclusion The downregulation of p16 protein induced by promoter methylation of p16 gene may not contribute to early cancinogenesis, but may contribute to progression of breast cancer.

 

Keywords: Breast cancer p16, Promoter methylation, Prognosis 

 

Full Text:

PDF


References


Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med, 2003; 349 (21):2042-2054.

Jing F, Jun L. Yong Z, et al. Multigene methylation in serum of sporadic Chinese female breast cancer paitents as prognostic biomarker. Oncology ,2008; 75(1-2):60-66.

Geradts J, Wilson PA. High frequency of aberrant pl6 (INK4A) expression in human breast cancer. Am J Pathol, 1996;149(1): 15-20.

Dominguez G, Silva J, Garcia JM, et al. Prevalence of aberrant methylation of pllARF over pl6INK4a in some human primary tumors. Mutat Res,2003 ;530( 1-2);9-17.

Hu SL, Kong XY, Cheng ZD, et al. Promoter methylation of p16, Runx3, DAPK and CHFR genes is frequent in gastric carcinoma. Tunori, 2010; 96 (5); 726-733.

Pehlivan S, Artac M, Sever T, et al. Gene methylation of SFRP2, p16, DAPK 1, H/Cl and MGMT and KRAS mutation in sporadic colorectal cancer. Cancer Genet,2010;201 (2): 128-132.

Holst CR, Nuovo GJ, Esteller M,et al. Methylation of p16 (INKia) promoters occurs in vivo in histologically normal human mammary epithelia. Cancer Res, 2003; 63 ( 7 ); 1596- 1601.

Wang L, Tang L, Xie R, et al. 16 promoter hypermethylation is associated with increased breast cancer risk. Mol Med Rep,2012;6(4) ;904-908.

Vallian S. Sedaghat M. Nassiri I, et al. Methylation status of p6INKA tumor suppressor gene in Iranian patients with sporadic breast cancer. J Cancer Res Clin Oncol.2009; 135(8): 991-996.

Tao MH. Shields PG, Nie J. et al. DNA hypermethylation and clinicopathological features in breast ancer: the Western New York P'xposures and Breast Cancer (WEB ) Study. Breast Cancer Res Treat,2009; 114(3) :559-568.

Raish M, Dhillon VS, Ahmad A, et al. Promoter hypermethylation in tumor suppressing genes p16 and FHIT and their relations estrogen receptor status in breast cancer patients from Northern India. Transl Oncol, 2009; 2 (4) ; 264- 70,

Lehn S, Fernf M, Jirstrfim K, et al. A non-functional retinoblastoma tumor suppressor ( RB ) pathway in premenopausal breast cancer is associated with resistance to tamoxifen. Cell Cycle,2011; 10(6) ;956-962.


Refbacks

  • There are currently no refbacks.