Bergner C C, Krause F S, Zugor V, Rith T, Schrott K M, Endele S, Engehausen D G
Department of Urology, University of Erlangen-Nuremberg, D - 91054 Erlangen, Germany.
Anticancer Res. 2007 Jul-Aug;27(4A):2071-4.
Prostate cancer is the second leading cause of death among men in Western countries. Genetic alterations of the estrogen receptor gene are known to be indicative of a higher risk of this disease. The estrogen receptor gene is found as two subtypes, alpha and beta. In this study the estrogen receptor alpha and beta genes were tested in 2 human prostate cancer cell lines: the hormone-sensitive PC-EW and the hormone-independent PC-OR.
Genomic DNA was isolated from 2 cell lines from metastatic prostate adenocarcinoma in hetero-transplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 and intron 1 of the human estrogen receptor gene alpha, and exons 1-9 of estrogen receptor gene beta.
No point mutations were detected in the ER gene subtypes of either cell line. Polymorphisms were found of ER-alpha in exon 1, intron 1, exon 3, 4, 5, intron 6 and exon 8 and of ER-beta in intron 2 and exon 9.
Point mutations of ER-alpha and -beta are not necessary for metastatic prostate cancer, alterations in different areas of the ER genes are more often found. These polymorphisms are a part of many genetic influences that accumulate to contribute to men's overall risk for developing prostate cancer.
在西方国家,前列腺癌是男性第二大死因。已知雌激素受体基因的基因改变表明患这种疾病的风险更高。雌激素受体基因有两种亚型,即α和β。在本研究中,对两种人前列腺癌细胞系进行了雌激素受体α和β基因检测:激素敏感的PC-EW和激素非依赖的PC-OR。
从异种移植到雄性无胸腺裸(nu/nu)Balb/c小鼠体内的转移性前列腺腺癌的两种细胞系中分离基因组DNA。通过对人雌激素受体基因α的外显子1-8和内含子1以及雌激素受体基因β的外显子1-9进行测序来进行突变筛查。
在任一细胞系的雌激素受体基因亚型中均未检测到点突变。在雌激素受体α的外显子1、内含子1、外显子3、4、5、内含子6和外显子8以及雌激素受体β的内含子2和外显子9中发现了多态性。
转移性前列腺癌并非必需雌激素受体α和β的点突变,雌激素受体基因不同区域的改变更常见。这些多态性是许多遗传影响的一部分,这些遗传影响累积起来会增加男性患前列腺癌的总体风险。