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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells
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Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells

机译：人雌激素受体α和β，孕激素受体和雄激素受体mRNA在正常和恶性卵巢上皮细胞中的表达

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Our understanding of the roles played by sex hormones in ovarian carcinogenesis has been limited by a lack of data concerning the mode of sex hormone action in human ovarian surface epithelial (HOSE) cells, the tissue of origin of >90 of ovarian cancers. We have compared the relative abundance of estrogen receptor (ER)ca, ER beta, progesterone receptor (PR), and androgen receptor (AR) mRNA in four primary cultures of HOSE cells obtained from postmeno- pausal women to those found in late serous adenocarcinoma primary cell cultures and established ovarian cancer cell lines. We observed coexpression of ERa and ER beta along with AR and PR transcripts in normal HOSE cells and disruption of ER alpha mRNA expression as well as dramatic down-regulation of PR and AR transcript expression in most ovarian cancer cells. In contrast, levels of ER beta mRNA were unaffected by the malignant state. Additionally, a novel mutation involving a 32-bp deletion in exon 1 of ER alpha transcripts was detected in the SKOV3 cell line. This mutation would explain why SKOV3 was reported to be ER-positive but estrogen- insensitive. Taken together, these findings suggest that estrogens, signaling via either or both ER subtypes, may play an indispensable role in regulating normal HOSE cell functions. Therefore, loss of ER alpha, PR, and AR mANA expression in HOSE cells may be responsible for neoplastic transformation in this cell type. In contrast, the roles played by ERP in normal and malignant HOSE cells remain elusive. Finally, the coexistence of mutated ER alpha mRNA and normal ER beta transcripts
机译：我们对性激素在卵巢癌发生中所起的作用的了解受到有关人类卵巢表面上皮（HOSE）细胞（> 90的卵巢癌起源组织）中性激素作用方式的数据的限制。我们已经比较了从绝经后妇女获得的四种HOSE细胞与晚期浆液性腺癌中发现的HOSE细胞的相对雌激素受体（ER）ca，ERβ，孕激素受体（PR）和雄激素受体（AR）mRNA的相对丰度。原代细胞培养和已建立的卵巢癌细胞系。我们观察到在正常的HOSE细胞中ERa和ER beta以及AR和PR转录本的共表达，以及在大多数卵巢癌细胞中ERαmRNA表达的破坏以及PR和AR转录本的急剧下调。相反，ERβmRNA的水平不受恶性状态的影响。此外，在SKOV3细胞系中检测到一个新突变，涉及ERα转录本外显子1的32 bp缺失。这种突变可以解释为什么据报道SKOV3是ER阳性但对雌激素不敏感的。综上所述，这些发现表明雌激素通过一种或两种ER亚型发出信号，可能在调节正常的HOSE细胞功能中起着不可或缺的作用。因此，HOSE细胞中ERα，PR和AR mANA表达的缺失可能是这种细胞类型中肿瘤转化的原因。相反，ERP在正常和恶性HOSE细胞中所起的作用仍然难以捉摸。最后，突变的ERαmRNA和正常ERβ转录本共存

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