ART-27, an androgen receptor coactivator regulated in prostate development and cancer.
Androgen receptor trapped clone-27 (ART-27) is a newly described transcriptional coactivator that binds to the N terminus of the androgen receptor (AR). Given the vital importance of AR signaling in prostate growth and differentiation, we investigated the role of ART-27 in these processes. Immunohistochemical studies indicate that ART-27 protein is expressed in differentiated epithelial cells of adult human prostate and breast tissue. In prostate, ART-27 is abundant in AR-positive prostate luminal epithelial cells, in contrast to the stroma, where cells express AR but not ART-27. The use of a rat model of androgen depletion/reconstitution indicates that ART-27 expression is associated with the elaboration of differentiated prostate epithelial cells. Interestingly, regulated expression of ART-27 in the androgen-sensitive LNCaP prostate cancer cell line inhibits androgen-mediated cellular proliferation and enhances androgen-mediated transcription of the prostate-specific antigen (PSA) gene. Consistent with a growth suppressive function, we show that ART-27 expression levels are negligible in human prostate cancer. Importantly, examination of ART-27 protein expression in early fetal prostate development demonstrates that ART-27 is detected only when the developing prostate gland has proceeded from a solid mass of undifferentiated cells to a stage in which differentiated luminal epithelial cells are evident. Thus, ART-27 is an AR cofactor shown to be subject to both cell type and developmental regulation in humans. Overall, the results suggest that decreased levels of ART-27 protein in prostate cancer tissue may occur as a result of de-differentiation, and indicate that ART-27 is likely to regulate a subset of AR-responsive genes important to prostate growth suppression and differentiation.
Taneja
Samir S
SS
Departments of Urology, New York University School of Medicine, New York, New York 10016, USA.
Ha
Susan
S
Swenson
Nicole K
NK
Torra
Inés Pineda
IP
Rome
Serge
S
Walden
Paul D
PD
Huang
Hong Ying
HY
Shapiro
Ellen
E
Garabedian
Michael J
MJ
Logan
Susan K
SK
D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001940:Breast / Q000166:cytology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D011467:Prostate / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
D000728:Androgens; D018797:Cell Cycle Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D015534:Trans-Activators; C118920:UXT protein, human