Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell lines.
BACKGROUND
In prostate cancer cell lines, androgen receptor (AR) coactivators modulate the transcriptional activity of AR. However, very little is known about their expression in normal prostate tissue and during progression to cancer.


METHODS
AR and coactivators ARA54, ARA55, ARA70, and SRC1 RNA were analyzed by RT-PCR in normal and tumoral tissues of the same prostate, in prostate cell lines, and after hormonal treatments of prostate epithelial cells.


RESULTS
AR-coactivators were expressed in normal and tumoral tissues and in cultured prostate cells; only ARA55 expression was decreased in tumoral relative to normal tissue of all seven prostates analyzed. It was not expressed in LNCaP and DU145 cancer cells and low in PNT2 immortalized cells in which all coactivator's expression were down regulated by DHT and up regulated by E2. In addition, coactivator's expression was increased in hyperplastic relative to normal prostate fibroblasts.


CONCLUSIONS
ARA55 is both an AR coactivator and a focal adhesion protein (Hic-5). Its role in the progression of prostate carcinoma may therefore involve these two different functions. Its decrease in cancer tissue suggests that it plays a different role than that expected, namely, facilitate cell proliferation and therefore mobility and metastasis.
Mestayer
C
C
Laboratoire de Recherche sur la Physiologie et la Pathologie Gonadique, Service d'Endocrinologie et Médecine de la Reproduction, Faculté de médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France.
Blanchère
M
M
Jaubert
F
F
Dufour
B
B
Mowszowicz
I
I
D002277:Carcinoma / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000494:pharmacology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004273:DNA, Neoplasm / Q000032:analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008297:Male; D009362:Neoplasm Metastasis; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000096:biosynthesis*; D015534:Trans-Activators / Q000494:pharmacology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; C118499:RNF14 protein, human; D011944:Receptors, Androgen; C490351:TGFB1I1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors