Expression and function of androgen receptor coactivator p44/Mep50/WDR77 in ovarian cancer.
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.
Department of Pathology, New York University School of Medicine, New York, New York, United States of America.
Martin
M
Ligr
Ruzeen Rohintan
RR
Patwa
Garrett
G
Daniels
Lorraine
L
Pan
Xinyu
X
Wu
Yirong
Y
Li
Liantian
L
Tian
Zhenxing
Z
Wang
Ruliang
R
Xu
Jingjing
J
Wu
Fan
F
Chen
Jinsong
J
Liu
Jian-Jun
JJ
Wei
Peng
P
Lee
D000728:Androgens / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D000728:Androgens; D004967:Estrogens; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D014157:Transcription Factors; C478359:WDR77 protein, human