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Expression and Function of Androgen Receptor Coactivator p44/Mep50/WDR77 in Ovarian Cancer

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
10
Identifiers
DOI: 10.1371/journal.pone.0026250
Keywords
  • Research Article
  • Biology
  • Molecular Cell Biology
  • Signal Transduction
  • Membrane Receptor Signaling
  • Hormone Receptor Signaling
  • Signaling In Cellular Processes
  • Transcriptional Signaling
  • Medicine
  • Diagnostic Medicine
  • Pathology
  • General Pathology
  • Molecular Pathology
  • Clinical Pathology
  • Obstetrics And Gynecology
  • Gynecologic Cancers
  • Oncology
  • Cancers And Neoplasms
  • Gynecological Tumors
  • Ovarian Cancer
  • Basic Cancer Research
Disciplines
  • Biology

Abstract

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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