Syeed Nidda, Syed Sameer A, Hamid Arif, Shah Zafar A, Afroze Dil, Rasool Roohi, Siddiqi Mushtaq A
Department of Immunology and Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Kashmir 190011, India.
Mol Med Rep. 2010 Sep-Oct;3(5):883-7. doi: 10.3892/mmr.2010.348. Epub 2010 Jul 26.
Promoter hypermethylation is a marginal approach to inactivating tumor suppressor genes in cancer. DNA hypermethylation is a well-recognized epigenetic malfunction observed in several malignancies, most predominantly in prostate cancer. Aberrant DNA methylation patterns are considered to be the earliest somatic genome changes in prostate cancer. The function of promoter hypermethylation in malignant transformation of the prostate has been widely studied, from its presence in benign hyperplasia (BHP) to development and to the advanced stages of tumor formation. In the present study, we examined the promoter hypermethylation status of the glutathione S-transferase P1 (GSTP1) and RASSF1A genes in 45 BHP samples, 50 proven prostate tumor samples and 80 normal samples. Hypermethylated GSTP1 was found in 29/50 (58.0%) prostate carcinoma cases and 12/45 (26.6%) BHP cases. The RASSF1A gene was methylated in 17/50 (34.0%) prostate cancer samples and 7/45 (15.5%) BHP samples. On the basis of these findings, we propose that the epigenetic regulation of the GSTP1 and RASSF1A genes through promoter hypermethylation may play a crucial role in the progression of prostate cancer, and has probable involvement in BHP.
启动子高甲基化是癌症中使肿瘤抑制基因失活的一种边缘方法。DNA高甲基化是在多种恶性肿瘤中观察到的一种公认的表观遗传功能障碍，在前列腺癌中最为常见。异常的DNA甲基化模式被认为是前列腺癌中最早的体细胞基因组变化。从其在良性增生（BHP）中的存在到肿瘤形成的发展和晚期阶段，启动子高甲基化在前列腺恶性转化中的作用已得到广泛研究。在本研究中，我们检测了45份BHP样本、50份经证实的前列腺肿瘤样本和80份正常样本中谷胱甘肽S-转移酶P1（GSTP1）和RASSF1A基因的启动子高甲基化状态。在29/50（58.0%）的前列腺癌病例和12/45（26.6%）的BHP病例中发现了GSTP1高甲基化。RASSF1A基因在17/50（34.0%）的前列腺癌样本和7/45（15.5%）的BHP样本中发生甲基化。基于这些发现，我们提出通过启动子高甲基化对GSTP1和RASSF1A基因进行表观遗传调控可能在前列腺癌的进展中起关键作用，并且可能与BHP有关。
