Inhibition of tumorigenic potential and prostate-specific antigen expression in LNCaP human prostate cancer cell line by 13-cis-retinoic acid.
Prostate-specific antigen (PSA) is a member of the kallikrein family and has been an important biological marker for prostate cancer. The mechanisms regulating PSA expression in prostatic cancer cells are unclear. The present study was designed to elucidate the role of 13-cis-retinoic acid (RA) in regulation of PSA and the tumorigenic potential of the human prostate cancer cell line LNCaP. The growth regulation of LNCaP cells was examined by DNA synthesis and doubling time. The tumorigenic potential of prostate cancer cells was analyzed by soft agar colony-forming assay, in vitro invasion assay, type IV collagenase assay and binding to extracellular matrix assay. The nuclear receptors for retinoic acid (RAR alpha, -beta, -gamma and RXR alpha, -beta, -gamma) as well as PSA mRNA were determined by Northern blot using specific oligonucleotide probes. Our results suggest that 13-cis-RA significantly inhibits PSA secretion and expression both at the mRNA and protein levels compared with untreated cells. Electron microscopic studies suggest that after 13-cis-RA treatment, cells become more differentiated as they contain lumina, lined by plasma membrane and microvilli. Prostate cancer cell growth and tumorigenic potential after 13-cis-RA treatment was significantly decreased compared with controls. Nude mice tumorigenicity studies showed that 13-cis-RA-treated cells produced significantly smaller tumors compared with untreated cell tumors. There was also a significant increase in the expression of RXRa mRNA after 13-cis-RA treatment compared with untreated cells.
Dahiya
R
R
Department of Urology, University of California, San Francisco.
Park
H D
HD
Cusick
J
J
Vessella
R L
RL
Fournier
G
G
Narayan
P
P
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015474:Isotretinoin / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008854:Microscopy, Electron; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005353:Fibronectins; D007797:Laminin; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D003094:Collagen; D017430:Prostate-Specific Antigen; D015474:Isotretinoin