Effect of androgens on different breast cancer cells co-cultured with or without breast adipose fibroblasts
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- 作者：Suthat Chottanapund ; Majorie B.M. Van Duursen ; Panida Navasumrit ; Potchanee Hunsonti ; Supatchaya Timtavorn ; Mathuros Ruchirawat ; Martin Van den Berg
- 关键词：Breast adipose fibroblasts ; Breast tumor cells ; Co-culture ; Estrogen receptor ; Androgens ; Cell proliferation ; pS2 ; Ki-67 ; Aromatase
- 刊名：The Journal of Steroid Biochemistry and Molecular Biology
- 出版年：November, 2013
- 年：2013
- 卷：138
- 期：Complete
- 页码：54-62
- 全文大小：1769 K
文摘
About 70% of breast tumors express androgen receptors. In addition, there is clinical evidence suggesting that androgens can inhibit mammary epithelial proliferation. Vice versa, there is also significant evidence indicating that androgens can increase the risk of breast cancer via multiple mechanisms, e.g. direct conversion to estrogens that can bind to the estrogen receptor and thereby stimulate cell proliferation. We examined the effect of testosterone (T) and dihydroxytestosterone (DHT) on cell proliferation, pS2 and Ki-67 expression in three different breast cancer cell lines alone or in co-culture with primary human breast adipose fibroblasts (BAFs) obtained from breast cancer patients. In the co-cultures, T induced cell proliferation, pS2 and Ki-67 expression in the estrogen receptor positive (ER+) MCF-7 and T47D cells. This was not observed in the (ER鈭?/sup>) MDA-MB-231 cells. The differences might be explained by the high expression of aromatase, which converts androgens to estrogens in BAFs followed by ER-mediated cell proliferation. In line with this absence of increased cell proliferation, pS2 and Ki-67 expression was observed in the presence of DHT, which is not a substrate for aromatase. In contrast, DHT caused a significant suppression of cell proliferation (68% and 38%), pS2 and Ki-67 expression in the (ER+) MCF-7 and T47D cells. More importantly, DHT decreased cell proliferation in (ER鈭?/sup>) MDA-MB-231 cells by 38%. The results suggest that androgens that cannot be aromatized, like DHT, may provide a perspective for treatment of breast cancer patients, especially those with triple negative breast cancer.