P A Shaw1, P V Rittenberg, T J Brown. 1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: 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. METHODS: Twenty invasive ovarian carcinomas and four nonmalignant ovaries were tested for ARA70 mRNA expression by in situ hybridization using a 35S-labeled riboprobe. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. METHODS: Twenty invasive ovarian carcinomas and four nonmalignant ovaries were tested for ARA70 mRNA expression by in situ hybridization using a 35S-labeled riboprobe. RESULTS: The probe was first assessed using a sample of humanbenign 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. CONCLUSION: 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.
Authors: Francesmary Modugno; Robin Laskey; Ashlee L Smith; Courtney L Andersen; Paul Haluska; Steffi Oesterreich Journal: Endocr Relat Cancer Date: 2012-11-09 Impact factor: 5.678