TY - JOUR
T1 - Expression and function of androgen receptor coactivator p44/MEP50/WDR77 in ovarian cancer
AU - Ligr, Martin
AU - Patwa, Ruzeen Rohintan
AU - Daniels, Garrett
AU - Pan, Lorraine
AU - Wu, Xinyu
AU - Li, Yirong
AU - Tian, Liantian
AU - Wang, Zhenxing
AU - Xu, Ruliang
AU - Wu, Jingjing
AU - Chen, Fan
AU - Liu, Jinsong
AU - Wei, Jian Jun
AU - Lee, Peng
PY - 2011/10/13
Y1 - 2011/10/13
N2 - Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.
AB - Hormones, including estrogen and progesterone, and their receptors play an important role in the development and progression of ovarian carcinoma. Androgen, its receptor and coactivators have also been implicated in these processes. p44/Mep50/WDR77 was identified as a subunit of the methylosome complex and lately characterized as a steroid receptor coactivator that enhances androgen receptor as well as estrogen receptor-mediated transcriptional activity in a ligand-dependent manner. We previously described distinct expression and function of p44 in prostate, testis, and breast cancers. In this report, we examined the expression and function of p44 in ovarian cancer. In contrast to findings in prostate and testicular cancer and similar to breast cancer, p44 shows strong cytoplasmic localization in morphologically normal ovarian surface and fallopian tube epithelia, while nuclear p44 is observed in invasive ovarian carcinoma. We observed that p44 can serve as a coactivator of both androgen receptor (AR) and estrogen receptor (ER) in ovarian cells. Further, overexpression of nuclear-localized p44 stimulates proliferation and invasion in ovarian cancer cells in the presence of estrogen or androgen. These findings strongly suggest that p44 plays a role in mediating the effects of hormones during ovarian tumorigenesis.
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U2 - 10.1371/journal.pone.0026250
DO - 10.1371/journal.pone.0026250
M3 - Article
C2 - 22022581
AN - SCOPUS:80054124577
SN - 1932-6203
VL - 6
JO - PLoS One
JF - PLoS One
IS - 10
M1 - e26250
ER -
