TY - JOUR
T1 - Distinct function of androgen receptor coactivator ARA70α and ARA70β in mammary gland development, and in breast cancer
AU - Wu, Xinyu
AU - Chen, Fei
AU - Sahin, Aysegul
AU - Albarracin, Constance
AU - Pei, Zhiheng
AU - Zou, Xuanyi
AU - Singh, Baljit
AU - Xu, Ruliang
AU - Daniels, Garrett
AU - Li, Yirong
AU - Wei, Jianjun
AU - Blake, Marvin
AU - Schneider, Robert J.
AU - Cowin, Pamela
AU - Lee, Peng
N1 - Funding Information:
Acknowledgments This project is supported by grants from Susan Komen Foundation and DOD BCRP BC062835 to P.L., a New York State Department of Health postdoctoral fellowship award to F.C and DOD BCRP BC074763 and R21CA122905 to P.C.
PY - 2011/7
Y1 - 2011/7
N2 - 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 ARA70α functions as a tumor suppressor gene and that ARA70β functions as an oncogene in prostate cancer. Here we show that both ARA70α and ARA70β function as AR and estrogen receptor (ER) coactivators in breast cancer cells. However, ARA70α and ARA70β serve different functions in mammary gland development and breast cancer tumorigenesis. We observed hypoplastic development of mammary glands in MMTV driven ARA70α transgenic mice and overgrowth of mammary glands in ARA70β transgenic mice at virgin and pregnant stages. We determined that ARA70α inhibited cell proliferation, and that ARA70β 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 ARA70β strongly enhanced the invasive ability of MCF7 breast cancer cells in in vitro Matrigel assays. Significantly, decreased ARA70α expression is associated with increased tendency of breast cancer metastasis. In summary, ARA70α and ARA70β have distinct effects in mammary gland development and in the progression of breast cancer.
AB - 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 ARA70α functions as a tumor suppressor gene and that ARA70β functions as an oncogene in prostate cancer. Here we show that both ARA70α and ARA70β function as AR and estrogen receptor (ER) coactivators in breast cancer cells. However, ARA70α and ARA70β serve different functions in mammary gland development and breast cancer tumorigenesis. We observed hypoplastic development of mammary glands in MMTV driven ARA70α transgenic mice and overgrowth of mammary glands in ARA70β transgenic mice at virgin and pregnant stages. We determined that ARA70α inhibited cell proliferation, and that ARA70β 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 ARA70β strongly enhanced the invasive ability of MCF7 breast cancer cells in in vitro Matrigel assays. Significantly, decreased ARA70α expression is associated with increased tendency of breast cancer metastasis. In summary, ARA70α and ARA70β have distinct effects in mammary gland development and in the progression of breast cancer.
KW - AR coactivator
KW - ARA70
KW - Breast cancer
KW - Mammary gland development
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U2 - 10.1007/s10549-010-1131-5
DO - 10.1007/s10549-010-1131-5
M3 - Article
C2 - 20814820
AN - SCOPUS:79959694638
SN - 0167-6806
VL - 128
SP - 391
EP - 400
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 2
ER -