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

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 liganddependent 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.

The Role of Androgen Receptor Signaling in Ovarian Cancer

“…Second, DHT (e.g., 10–100 nM) considerably induced cell proliferation of established AR-positive lines [26,47,71,72,73,74], and anti-androgens, including flutamide/hydroxyflutamide and bicalutamide, blocked the stimulatory effects of DHT [47,72,73,75]. Other androgens, such as testosterone [47], androstenedione [74], and a synthetic androgen methyltrienolone [76], were also shown to increase the proliferation of cancer cells. Third, DHT increased S-phase population in a primary culture [55] or OVCAR3 [73].…”

“…It was additionally shown that DHT induced cell motility and invasion of an ovarian cancer line [79]. Methyltrienolone [76] and another AR ligand, medroxyprogesterone [80], also increased the ability of cell invasion of AR-positive ovarian cancer lines, although the latter is classified as a progestin. All of these studies have thus demonstrated in vitro and in vivo data indicating that androgens promote cell proliferation/invasion of ovarian cancer via the AR pathway.…”

“…p44 is a 44 kDa AR-interacting protein originally identified as a subunit of the methylosome complex [76]. An immunohistochemical study showed that cytoplasmic p44 was more strongly expressed in normal-appearing ovarian surface epithelium, while nuclear p44 expression was predominantly observed in ovarian carcinoma [76].…”

Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation

“…Studies further indicate that the interaction of the AR-ligand and co-activator plays an important role in gene expression. The AR co-activator, p44/Mep50, a subunit of the methylosome complex, enhances AR-mediated transcription activity in a ligand-dependent manner [22,23]. While it may act as a nuclear co-activator in breast cancer cells, p44 is also present in substantial quantities in the cytoplasm of terminal ductal lobular units [22,23].…”

“…The AR co-activator, p44/Mep50, a subunit of the methylosome complex, enhances AR-mediated transcription activity in a ligand-dependent manner [22,23]. While it may act as a nuclear co-activator in breast cancer cells, p44 is also present in substantial quantities in the cytoplasm of terminal ductal lobular units [22,23]. When overexpressed by MCF7 breast cancer cells, p44 has been shown to enhance proliferation and invasiveness [22].…”