PKCdelta requires p53 for suppression of the transformed phenotype in human colon cancer cells.
We have previously demonstrated that the delta isoform of Protein Kinase C (PKCdelta) acts as a tumor suppressor in HCT116 human colon cancer cells, and that p21(waf1/cip1) is an essential downstream effector of PKCdelta. Our data suggested that p53 might also be involved in the suppression of the neoplastic phenotype induced by PKCdelta. Here we show that homozygous knockout of p53 renders the HCT116 cell line unresponsive to PKCdelta overexpression. Whereas reconstitution of p53 alone did not modify the morphology and growth properties of HCT116/p53null cells, overexpression of both p53 and PKCdelta induced a number of alterations indicating suppression of the transformed phenotype. Interestingly, PKCdelta was ineffective when overexpressed in HT29 cells, a human colon cancer line characterized by the Arg273His dominant-negative mutation of p53. Thus, our data indicate that wild-type p53 is an essential effector of PKCdelta in human colon cancer cells.
Perletti
Gianpaolo
G
Department of Structural and Functional Biology, University of Insubria, Via A. Da Giussano, 12, 21052 Varese/Busto Arsizio, Italy. gianpaolo.perletti@uninsubria.it
Marras
Emanuela
E
Osti
Daniela
D
Felici
Lara
L
Zaro
Sabrina
S
de Eguileor
Magda
M
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005799:Genes, Dominant; D016158:Genes, p53; D045325:HCT116 Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D010641:Phenotype; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051745:Protein Kinase C-delta; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta