Df. Liu et Sa. Rabbani, INDUCTION OF URINARY PLASMINOGEN-ACTIVATOR BY RETINOIC ACID RESULTS IN INCREASED INVASIVENESS OF HUMAN PROSTATE-CANCER CELLS PC-3, The Prostate, 27(5), 1995, pp. 269-276
Overproduction of uPA by prostate cancer cells in vivo results in tumo
r invasiveness and osteoblastic skeletal metastasis due to its mitogen
ic actions in osteoblasts. In the present study we have examined the e
ffect of several growth factors and steroid hormones on regulating uPA
gene expression in the human prostate cancer cell line (PC-3). Treatm
ent of these cells with dexamethasone (Dex) caused a decrease, whereas
epidermal growth factor (EGF) and fetal bovine serum (FBS) increased
uPA expression in a dose-dependent manner. Trans retinoic acid (RA) al
so induced uPA mRNA and protein production in a dose-dependent manner
(10(-6) to 10(-9) M). This increase was seen as early as 2 hr of treat
ment until 48 hr. Dex treatment resulted in decreased tumor cells inva
siveness, whereas exposure to EGF and RA caused an increase in the inv
asive capacity of PC-3 cells. These studies should help to better unde
rstand the control mechanism of uPA expression in prostate cancer, whe
re uPA has been implicated as a major pathogenetic factor. (C) 1995 Wi
ley-Liss, Inc.