title: Altered growth regulation and enhanced tumorigenicity of NIH 3T3 fibroblasts transfected with protein kinase C-I cDNA.
abstract: Transfection of NIH 3T3 cells with plasmids containing rat brain protein kinase C-I (PKC-I) cDNA controlled by strong viral promoter/enhancer elements led to PKC-I gene expression as assessed by Northern analysis, cellular binding of phorbol ester, immunoblotting of cellular PKC, and membrane-associated PKC activity. While transfection did not induce foci, altered growth regulation was observed in established transfectant lines: transfectants displayed reduced dependence on serum for growth, grew to higher saturation densities, and displayed enhanced tumorigenicity when inoculated into nude mice. Continued high-level expression of PKC-I, however, may not be obligatory for the malignant phenotype in vivo. Tumors that retained transfected sequences had lower PKC-I transcript levels than the parental in vitro lines, suggesting an in vivo modulation. Our data show that PKC-I dysregulation leads to altered cell growth regulation and may be functionally equivalent to the action of tumor promoters.
authors.affiliation: Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: D A
authors.initials: DA
authors.lastname: Persons
authors.forename: W O
authors.initials: WO
authors.lastname: Wilkison
authors.forename: R M
authors.initials: RM
authors.lastname: Bell
authors.forename: O J
authors.initials: OJ
authors.lastname: Finn
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D004247:DNA; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D007527:Isoenzymes; D010703:Phorbol Esters; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D004247:DNA; D011493:Protein Kinase C