title: Evaluation of the chemopreventive potential of retinoids using a novel in vitro human prostate carcinogenesis model.
abstract: The prevalence of prostatic intraepithelial neoplasia (PIN) and latent prostatic carcinoma, representing multiple steps in carcinogenesis and progression to invasive carcinoma, makes them relevant targets for prevention. A unique family of human prostate epithelial cell lines, which mimic steps in prostate carcinogenesis and progression, were used to evaluate the chemopreventive potential of all-trans-retinoic acid (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR). The effects of RA and 4-HPR on anchorage-dependent growth of an immortalized, non-tumorigenic cell line RWPE-1 and two tumorigenic cell lines, WPE1-NB14 and WPE1-NB11, derived from RWPE-1 by exposure to N-methyl-N-nitrosourea (MNU), were examined. Both tumorigenic cell lines grow more rapidly than the parent RWPE-1 cell line in monolayer culture. Further, while RWPE-1 cells do not form colonies in agar, both tumorigenic cell lines do, with a colony forming efficiency (CFE) of 1.85 and 2.04% for WPE1-NB14 and WPE1-NB11 cells, respectively. Both RA and 4-HPR inhibited anchorage-dependent growth of all cell lines and anchorage-independent growth of WPE1-NB14 and WPE1-NB11 cells, in a dose-dependent manner, however, 10 times more RA than 4-HPR was required to produce the same effect. RWPE-1 cells are not invasive but WPE1-NB11 cells are significantly more invasive than WPE1-NB14 cells. Both RA and 4-HPR inhibited invasion in vitro by WPE1-NB11 and WPE1-NB14 cells where the more malignant WPE1-NB11 cells showed greater inhibition of invasion by 4-HPR than by RA. Overall, 4-HPR was more effective than RA in inhibiting growth and invasion but the response varied amongst the cell lines. These three cell lines mimic progressive steps in carcinogenesis and progression, from immortalized, non-tumorigenic RWPE-1 cells, to the less malignant WPE1-NB14 to the more malignant WPE1-NB11 cells, and provide powerful models for studies on secondary and tertiary prevention, i.e. promotion and progression stages, respectively, of prostate cancer.
authors.affiliation: Department of Zoology, Michigan State University, S350 Plant Biology Building, East Lansing, MI, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Quader
authors.forename: D
authors.initials: D
authors.lastname: Bello-DeOcampo
authors.forename: D E
authors.initials: DE
authors.lastname: Williams
authors.forename: H K
authors.initials: HK
authors.lastname: Kleinman
authors.forename: M M
authors.initials: MM
authors.lastname: Webber
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D018890:Chemoprevention; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009152:Mutagenicity Tests; D009368:Neoplasm Transplantation; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D012176:Retinoids / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D012176:Retinoids; D008770:Methylnitrosourea