Prostasin serine protease inhibits breast cancer Invasiveness and is transcriptionally regulated by promoter DNA methylation
Prostasin serine protease inhibits breast cancer Invasiveness and is transcriptionally regulated by promoter DNA methylation
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DOI：
10.1002/ijc.1601
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发表时间：
2002-01-20
影响因子：
6.4
通讯作者：
Chai, KX
中科院分区：
文献类型：
--
作者：
Chen, LM;Chai, KX
我们已经证明，前列腺素丝氨酸蛋白酶在高级别前列腺癌中下调，并在强制重新表达时抑制前列腺癌细胞系的侵袭性。在我们的研究中，前列腺素在正常乳腺上皮细胞(NHMEC)、低侵袭性乳腺癌细胞系MCF-7和非转移性乳腺癌细胞系MDA-MB-453中表达，而在高侵袭性和非转移性乳腺癌细胞系MDA-MB-231和MDA-MB-435s中不表达。在MDA-MB-231和MDA-MB-435s中强制重新表达前列腺素可使任一细胞系的体外侵袭力降低50%。对前列腺素基因启动子和第一外显子的检测显示，含有转录调控元件的GC富集区。对前列腺素基因启动子和外显子I区域在NHMEC和癌细胞中的DNA甲基化进行了研究。结果揭示了这些细胞中与前列腺素表达相关的甲基化模式。去甲基化和组蛋白脱乙酰酶抑制可使MDA-MB-231和MDA-MB-435s细胞中前列腺素mRNA的表达重新激活。这些结果表明，前列腺素在乳腺癌细胞中的表达可能受DNA甲基化的调节，前列腺素表达缺失可能与乳腺癌的侵袭性和转移潜能有关。(C)2002年Wiley-Liss，Inc.
We have shown that prostasin serine protease is downregulated in high-grade prostate tumors and inhibits invasiveness of prostate cancer cell lines upon enforced reexpression. In our study, prostasin mRNA and protein were shown to be expressed in normal human mammary epithelial cells (NHMEC), the poorly invasive breast carcinoma cell line MCF-7 and the nonmetastatic breast carcinoma cell line MDA-MB-453, but absent in highly invasive and rn astatic breast carcinoma cell lines MDA-MB-231 and MDA-MB-435s. Enforced reexpression of prostasin in MDA-MB-231 and MDA-MB-435s reduced the in vitro invasiveness of either cell line by 50%. Examination of the prostasin gene promoter and first exon revealed a GC-enriched region that contains transcription regulatory elements. The promoter and exon I region of the prostasin gene was investigated for DNA methylation in NHMEC and the carcinoma cell lines. The results revealed a methylation pattern that correlates with prostasin expression in these cells. Demethylation coupled with histone deacetylase inhibition resulted in reactivated expression of the prostasin mRNA in MDA-MB-231 and MDA-MB-435s cells. These results suggest that prostasin expression in breast cancer cells may be regulated by DNA methylation and that an absence of prostasin expression may contribute to breast cancer invasiveness and metastatic potential. (C) 2002 Wiley-Liss, Inc.