Induction of urinary plasminogen activator by retinoic acid results in increased invasiveness of human prostate cancer cells PC-3.
Overproduction of uPA by prostate cancer cells in vivo results in tumor invasiveness and osteoblastic skeletal metastasis due to its mitogenic actions in osteoblasts. In the present study we have examined the effect of several growth factors and steroid hormones on regulating uPA gene expression in the human prostate cancer cell line (PC-3). Treatment 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) also 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 treatment until 48 hr. Dex treatment resulted in decreased tumor cells invasiveness, whereas exposure to EGF and RA caused an increase in the invasive capacity of PC-3 cells. These studies should help to better understand the control mechanism of uPA expression in prostate cancer, where uPA has been implicated as a major pathogenetic factor.
D000230:Adenocarcinoma / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D002417:Cattle; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D012710:Serum Albumin, Bovine; D014212:Tretinoin; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D014568:Urokinase-Type Plasminogen Activator