Distinct function of androgen receptor coactivator ARA70a and ARA70b in mammary gland development, and in breast cancer
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Xinyu Wu Fei Chen Aysegul Sahin Constance Albarracin Zhiheng Pei Xuanyi Zou Baljit Singh Ruliang Xu Garrett Daniels Yirong Li Jian
- چاپ و سال / کشور: 2010
Description
Steroid receptor coactivators are important in regulating the function of the receptors in endocrine organ development and in cancers, including breast. Androgen receptor (AR) coactivator ARA70, was first identified as a gene fused to the ret oncogene and later characterized as an AR coactivator. We previously reported that the full length ARA70a functions as a tumor suppressor gene and that ARA70b functions as an oncogene in prostate cancer. Here we show that both ARA70a and ARA70b function as AR and estrogen receptor (ER) coactivators in breast cancer cells. However, ARA70a and ARA70b serve different functions in mammary gland development and breast cancer tumorigenesis. We observed hypoplastic development of mammary glands in MMTV driven ARA70a transgenic mice and overgrowth of mammary glands in ARA70b transgenic mice at virgin and pregnant stages. We determined that ARA70a inhibited cell proliferation, and that ARA70b promotes proliferation in MCF7 breast cancer cells. These effects were observed in hormone-free media, or in media with androgen or estrogen, though to varying degrees. Additionally, we observed that ARA70b strongly enhanced the invasive ability of MCF7 breast cancer cells in in vitro Matrigel assays. Significantly, decreased ARA70a expression is associated with increased tendency of breast cancer metastasis. In summary, ARA70a and ARA70b have distinct effects in mammary gland development and in the progression of breast cancer.
Breast Cancer Res Treat (2011) 128:391–400 Received: 12 July 2010 / Accepted: 13 August 2010 / Published online: 3 September 2010 Springer Science+Business Media, LLC. 2010
