title: Isolation and characterization of transforming growth factor beta response variants from human prostatic tumor cell lines.
abstract: In this study we examined the relation between the response to transforming growth factor beta (TGF beta 1) in vitro and the growth in vivo of 1-LN-PC3-1A (1-LN) human prostatic carcinoma cells. 1-LN cells resistant to the growth-inhibitory effects of TGF beta 1 were isolated after exposure to 2 ng/ml TGF beta 1 in an anchorage-independent growth assay. Cloning of TGF beta 1-resistant and -sensitive populations produced 2 clones (R2-6 and 1-LN clone 4), which maintained relatively stable resistance or sensitivity, respectively, in the absence of TGF beta 1 for up to 12 passages. Colony formation by the R2-6 cells in the presence of TGF beta 1 was 2-10 times greater than that of 1-LN clone 4, depending upon the TGF beta 1 concentration. Injection of 1 x 10(5) R2-6 cells into athymic nude mice produced tumors with a significantly shorter latency interval as compared with 1-LN clone 4 tumors (P < 0.0001). Western immunoblotting showed that higher levels of latent TGF beta 1 protein were secreted into the culture medium by 1-LN clone 4 cells. Acidified conditioned media from both clones inhibited mink lung epithelial cell DNA synthesis. Neutralizing monoclonal antibody to TGF beta 1 but not TGF beta 2 abrogated this inhibitory effect. Comparison of the different sensitive and resistant clones showed that in vitro sensitivity to TGF beta 1 and in vivo tumor latency interval were not invariably correlated. Thus, the TGF beta 1 response phenotype in vitro was not always predictive of growth delay in vivo.
authors.affiliation: Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: R G
authors.initials: RG
authors.lastname: Watts
authors.forename: J L
authors.initials: JL
authors.lastname: Ware
mesh_terms: D000818:Animals; D001681:Biological Assay; D015197:Carcinogenicity Tests; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008907:Mink; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016212:Transforming Growth Factor beta