Villa E, Camellini L, Dugani A, Zucchi F, Grottola A, Merighi A, Buttafoco P, Losi L, Manenti F
Chair of Gastroenterology, University of Modena, Italy.
Cancer Res. 1995 Feb 1;55(3):498-500.
The development of hepatocellular carcinoma (HCC) in addition to cirrhosis affects males in a significantly higher proportion than females. Liver estrogen receptors increase when HCC develops in males; however, these tumors usually respond poorly to antiestrogens. We have, therefore, hypothesized that, similar to breast cancer, estrogen receptors in males with HCC may be mutated. Variant estrogen receptor transcripts (lacking exon 5 of the hormone binding domain) were investigated by reverse transcription-PCR in 14 patients (7 males and 7 females) with HCC. While females mostly displayed the wild-type transcript (both in peritumoral and in tumor liver tissue), males showed both transcripts in the cirrhotic tissue and almost only the variant in the tumor. As the variant ER transcripts when translated could give rise to truncated receptors still able to constitutively activate transcription, they may be key factors in favoring deregulated proliferation in the male liver.
除肝硬化外，肝细胞癌（HCC）的发生在男性中的比例显著高于女性。男性发生HCC时肝脏雌激素受体会增加；然而，这些肿瘤通常对抗雌激素反应不佳。因此，我们推测，与乳腺癌类似，患有HCC的男性体内的雌激素受体可能发生了突变。通过逆转录聚合酶链反应（RT-PCR）对14例HCC患者（7例男性和7例女性）的雌激素受体变体转录本（缺乏激素结合域的外显子5）进行了研究。女性大多表现为野生型转录本（在瘤旁和肿瘤肝组织中均如此），而男性在肝硬化组织中显示出两种转录本，在肿瘤中几乎只显示变体转录本。由于翻译后的变体ER转录本可能产生仍能组成性激活转录的截短受体，它们可能是促进男性肝脏增殖失控的关键因素。
