Sharma Gayatri, Mirza Sameer, Parshad Rajinder, Srivastava Anurag, Gupta Siddartha Datta, Pandya Pranav, Ralhan Ranju
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Tumour Biol. 2011 Feb;32(1):23-32. doi: 10.1007/s13277-010-0087-8. Epub 2010 Aug 10.
Maspin is a serine protease inhibitor with tumor-suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Previous studies indicate that the loss of Maspin expression is closely linked to aberrant methylation of the Maspin promoter. We examined the promoter methylation status of Maspin in tumor and corresponding serum of breast cancer patients. In addition, protein expression of this gene was also assessed to determine possible correlation between promoter hypermethylation and gene silencing. Further, we investigated the correlation of Maspin expression with vascular endothelial growth factor (VEGF-A) and MTA1 expression. Maspin methylation was analyzed by methylation-specific PCR in 100 invasive ductal breast carcinoma patients' tumors and circulating DNA in a prospective study. Promoter hypermethylation was correlated with expression of the encoded protein in tumors by immunohistochemistry. Significant correlation was observed between promoter hypermethylation of Maspin (r = +0.88; p ≤ 0.0001) in tumors and paired sera. Significant association was found between Maspin promoter hypermethylation and loss of its protein expression (p = 0.01, OR = 3.1, 95% CI = 1.3-7.4). The expression of VEGF-A and MTA1 was lower in tumors with high Maspin expression compared to tumors with loss of Maspin expression. Our results indicate that aberrant promoter methylation is associated with loss of Maspin immunoreactivity in breast cancer tissues. Further, loss of Maspin expression is significantly correlated with increased expression of VEGF-A and MTA1.
乳腺丝抑蛋白是一种具有肿瘤抑制活性的丝氨酸蛋白酶抑制剂。乳腺丝抑蛋白可在体内抑制肿瘤生长和转移，在体外抑制肿瘤细胞的运动和侵袭。先前的研究表明，乳腺丝抑蛋白表达缺失与乳腺丝抑蛋白启动子的异常甲基化密切相关。我们检测了乳腺癌患者肿瘤组织及相应血清中乳腺丝抑蛋白的启动子甲基化状态。此外，还评估了该基因的蛋白表达，以确定启动子高甲基化与基因沉默之间的可能相关性。此外，我们还研究了乳腺丝抑蛋白表达与血管内皮生长因子（VEGF-A）和MTA1表达之间的相关性。在一项前瞻性研究中，通过甲基化特异性PCR分析了100例浸润性导管癌患者肿瘤组织和循环DNA中的乳腺丝抑蛋白甲基化情况。通过免疫组织化学检测启动子高甲基化与肿瘤中编码蛋白表达的相关性。在肿瘤组织及其配对血清中，观察到乳腺丝抑蛋白启动子高甲基化之间存在显著相关性（r = +0.88；p≤0.0001）。发现乳腺丝抑蛋白启动子高甲基化与其蛋白表达缺失之间存在显著关联（p = 0.01，OR = 3.1，95%CI = 1.3 - 7.4）。与乳腺丝抑蛋白表达缺失的肿瘤相比，乳腺丝抑蛋白高表达的肿瘤中VEGF-A和MTA1的表达较低。我们的结果表明，启动子异常甲基化与乳腺癌组织中乳腺丝抑蛋白免疫反应性缺失有关。此外,乳腺丝抑蛋白表达缺失与VEGF-A和MTA1表达增加显著相关。
