title: Failure of wild-type or a mutant form of protein kinase C-alpha to transform fibroblasts.
abstract: A mutant form of the alpha-isoform of protein kinase C (PKC) was recently isolated from an ultraviolet radiation-induced murine fibrosarcoma cell line and reported to transform mouse BALB/c 3T3 fibroblasts on transfection. Four point mutations in the regulatory domain were assumed to be responsible for its oncogenicity and unusual preference for membrane localization. Here, we report that overexpression of the reported mutant PKC alpha complementary DNA in three fibroblast cell lines, including BALB/c 3T3, does not enable these cells to grow in soft agar or nude mice. In addition, this mutant PKC alpha form seems to be indistinguishable from the wild-type PKC alpha with respect to its dependence on cofactors, phorbol ester binding, subcellular distribution and its effects on growth and morphology. These results fail to confirm the previous study and indicate that overexpression of either the wild-type or the reported mutant form of PKC alpha does not transform rodent fibroblasts.
authors.affiliation: Comprehensive Cancer Center, Columbia University, New York, New York 10032.
authors.forename: C
authors.initials: C
authors.lastname: Borner
authors.forename: I
authors.initials: I
authors.lastname: Filipuzzi
authors.forename: I B
authors.initials: IB
authors.lastname: Weinstein
authors.forename: R
authors.initials: R
authors.lastname: Imber
mesh_terms: D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D005354:Fibrosarcoma / Q000201:enzymology; D015870:Gene Expression; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009154:Mutation; D011493:Protein Kinase C / Q000235:genetics*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate