Shaw P A, Rittenberg P V, Brown T J
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Gynecol Oncol. 2001 Feb;80(2):132-8. doi: 10.1006/gyno.2000.6068.
Androgens have been implicated in ovarian cancer and androgen receptor expression has been reported in 70-95% of ovarian adenocarcinomas, implying a role in ovarian cancer cell biology. Androgen receptor-associated protein 70 (ARA70) is a reported androgen receptor coactivator that enhances the transactivational potential of the androgen receptor up to 10-fold. Because ARA70 expression could amplify androgen action in ovarian cancer cells, we examined patient samples of ovarian cancer for ARA70 expression.
Twenty invasive ovarian carcinomas and four nonmalignant ovaries were tested for ARA70 mRNA expression by in situ hybridization using a 35S-labeled riboprobe.
The probe was first assessed using a sample of human benign prostatic hyperplasia. Expression was restricted to cells within the epithelial glands, which are known to express the highest levels of androgen receptor. In the nonmalignant ovary, ARA70 mRNA was expressed in moderate levels in thecal cells associated with antral follicles, with less labeling observed in granulosa cells and stroma. The surface epithelium was negative for ARA70 transcripts, with only low levels observed in occasional cells. In contrast, a high level of ARA70 expression was observed in 17 of the 20 ovarian carcinomas of various histological types. Labeling was associated with the tumor cells while little if any ARA70 mRNA was observed in stromal cells associated with the carcinoma.
These observations indicate that ARA70 expression is activated in invasive ovarian cancer tumor cells, and suggest that amplification of androgen action by ARA70 may be involved in the etiology/progression of this disease.
雄激素与卵巢癌有关，据报道70%-95%的卵巢腺癌中有雄激素受体表达，这意味着其在卵巢癌细胞生物学中发挥作用。雄激素受体相关蛋白70（ARA70）是一种已报道的雄激素受体共激活因子，可将雄激素受体的反式激活潜能提高至10倍。由于ARA70表达可能会增强卵巢癌细胞中的雄激素作用，我们检测了卵巢癌患者样本中的ARA70表达情况。
使用35S标记的核糖探针通过原位杂交检测20例浸润性卵巢癌和4例非恶性卵巢组织中的ARA70 mRNA表达。
首先使用人良性前列腺增生样本对探针进行评估。表达仅限于上皮腺体内的细胞，已知这些细胞表达最高水平的雄激素受体。在非恶性卵巢中，ARA70 mRNA在与窦状卵泡相关的卵泡膜细胞中中等水平表达，在颗粒细胞和基质中观察到的标记较少。表面上皮细胞ARA70转录本呈阴性，仅在偶尔的细胞中观察到低水平表达。相比之下，在20例不同组织学类型的卵巢癌中，有17例观察到高水平的ARA70表达。标记与肿瘤细胞相关，而在与癌相关的基质细胞中几乎未观察到ARA70 mRNA。
这些观察结果表明，ARA70表达在浸润性卵巢癌肿瘤细胞中被激活，提示ARA70介导的雄激素作用增强可能参与了该疾病的病因学/进展过程。
