Disturbed expression of phase I and phase II estrogen-metabolizing enzymes in endometrial cancer: Lower levels of CYP1B1 and increased expression of S-COMT
Disturbed expression of phase I and phase II estrogen-metabolizing enzymes in endometrial cancer: Lower levels of CYP1B1 and increased expression of S-COMT
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DOI：
10.1016/j.mce.2010.09.011
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Rizner, Tea Lanisnik
中科院分区：
文献类型：
--
作者：
Hevir, Neli;Sinkovec, Jasna;Rizner, Tea Lanisnik
采用实时荧光定量PCR技术检测38例子宫内膜癌组织及癌旁正常子宫内膜组织中雌激素代谢酶CYP1A1、CYP1A2、CYP1B1、CYP3A5、CYP3A7、SULT1A1、SULT1E1、SUL7281、COMT、UG72B7和GST P1基因的表达水平。CYP1B1和CYP3A7在子宫内膜癌中的表达水平显著降低，SULT 2B1、UG72B7和GST 1的表达水平显著升高，而COMT、CYP1A1、CYP3A5、SULT 1E1和SULT 2A1的表达无差异。用Western blotting和免疫组织化学染色检测CYP1B1和COMT蛋白，支持实时PCR分析。在癌性子宫内膜中检测到较低水平的CYP1B1，表明其在对照、癌前组织中的重要作用。此外，我们首次发现癌性子宫内膜中可溶性COMT的蛋白水平较高，而对照、癌前子宫内膜中膜结合COMT的水平较高。可溶性和膜结合COMT之间的比例变化的重要性仍需要在进一步的研究中进行评估。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Expression levels of genes encoding phase land phase II estrogen-metabolizing enzymes: CYP1A1, CYP1A2, CYP1B1, CYP3A5, CYP3A7, SULT1A1, SULT1E1, SUL7281, COMT, UG72B7, and GSTP1 were studied by real-time PCR in 38 samples of cancerous and adjacent control endometrium. We found significantly lower levels of CYP1B1 and CYP3A7, higher levels of SULT2B1, UG72B7 and GSTP1, and no differences in expression of COMT, CYP1A1, CYP3A5, SULT1E1 and SULT2A1 in the endometrial cancers. The CYP1B1 and COMT proteins were also examined by Western blotting and immunohistochemical staining, supporting the real-time PCR analysis. Lower levels of CYP1B1 detected in cancerous endometrium suggest its important role in control, precancerous tissue. Additionally, we showed for the first time higher protein levels of soluble COMT in cancerous endometrium, and higher levels of membrane-bound COMT in control, precancerous endometrium. The importance of the changed ratio between soluble and membrane-bound COMT still needs to be evaluated in further studies. (C) 2010 Elsevier Ireland Ltd. All rights reserved.