Androgen modulation of adhesion and antiadhesion molecules in PC-3 prostate cancer cells expressing androgen receptor.
The metastatic spread of cancer cells involves a complex process of detachment via antiadhesion molecules and attachment and migration through adhesion. In the prostate, androgens are generally thought to contribute to the development and progression of prostate cancer by promoting cell proliferation and survival through poorly defined mechanisms. We have reported previously that PC-3 prostate cancer cells, which are unresponsive to androgens, show androgen-dependent detachment and ultimately apoptosis when stably transfected with a full-length human androgen receptor (AR) cDNA. We now demonstrate that treatment of these cells with 5alpha-dihydrotestosterone (DHT) for 24 or 48 h increased the expression of antiadhesion mucin MUC-1 at the cell surface as detected by flow cytometry with two independent antibodies. This increase in protein was concordant with up-regulation of MUC-1 mRNA in the AR-transfected PC-3 sublines, as determined by quantitative RT-PCR. Treatment with DHT for 48 h also down-regulated the cell surface expression of alpha2beta1-integrin but having little effect on the levels of alpha3beta1- and alpha5beta1-integrins. Androgen also decreased, in a dose-dependent manner, the adhesion of AR-transfected PC-3 cells to collagen type I, which was shown to be specifically inhibited by blocking antibody to alpha2beta1-integrin. The present data demonstrate that DHT can modulate expression of adhesion and antiadhesion molecules and suggest that this effect of androgen might contribute to prostate cancer progression.
Evangelou
Andreas
A
Cancer and Blood Research Program, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Letarte
Michelle
M
Marks
Alexander
A
Brown
Theodore J
TJ
D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D024042:Collagen Type I / Q000494:pharmacology; D013196:Dihydrotestosterone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008297:Male; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D038981:Receptors, Collagen; D015854:Up-Regulation
D015815:Cell Adhesion Molecules; D024042:Collagen Type I; D016023:Integrins; D018396:Mucin-1; D012333:RNA, Messenger; D011944:Receptors, Androgen; D038981:Receptors, Collagen; D013196:Dihydrotestosterone