Protein kinase Cε is oncogenic in colon epithelial cells by interaction with the ras signal transduction pathway

We have shown previously that overexpression of the ε isoform of protein kinase C (PKCε) in rat colonic epithelial cells causes malignant transformation, possibly by interacting with the ras signal transduction pathway (Oncogene 12: 847, 1996). We have now performed experiments to examine certain ea...

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Veröffentlicht in:Oncogene 1998-06, Vol.16 (25), p.3345-3348
Hauptverfasser: PERLETTI, G. P, CONCARI, P, BRUSAFERRI, S, MARRAS, E, PICCININI, F, TASHJIAN, A. H
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container_end_page 3348
container_issue 25
container_start_page 3345
container_title Oncogene
container_volume 16
creator PERLETTI, G. P
CONCARI, P
BRUSAFERRI, S
MARRAS, E
PICCININI, F
TASHJIAN, A. H
description We have shown previously that overexpression of the ε isoform of protein kinase C (PKCε) in rat colonic epithelial cells causes malignant transformation, possibly by interacting with the ras signal transduction pathway (Oncogene 12: 847, 1996). We have now performed experiments to examine certain early steps in the ras signaling pathway. A marked increase of Raf-1 phosphorylation was detected in tumorigenic ras-transformed D/ras as well as in D/ε cells (overexpressing PKCε), compared to the nontumorigenic D/WT parental line. Moreover, in the PKCε-transformed D/ε cell line, stable transfection with a dominant-negative raf-1 (DNraf) sequence caused complete regression of the neoplastic phenotype. These results suggested that PKCε-induced transformation was associated with increased Raf-1 activation, and that DNraf could block the oncogenic effect of PKCε. Furthermore, transfection of D/WT cells with dominant-negative ras induced arrest of cell growth, and subsequent transfection with PKCε cDNA enhanced cell proliferation and induced neoplastic transformation. These results suggest that ras acts upstream of PKCε, and that overexpression of PKCε circumvents the block in cell proliferation caused by dominant-negative ras. We conclude that PKCε exerts its oncogenic activity in rat colonic cells by affecting the ras signaling cascade at the level of Raf-1 activation.
doi_str_mv 10.1038/sj.onc.1201871
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P ; CONCARI, P ; BRUSAFERRI, S ; MARRAS, E ; PICCININI, F ; TASHJIAN, A. H</creator><creatorcontrib>PERLETTI, G. P ; CONCARI, P ; BRUSAFERRI, S ; MARRAS, E ; PICCININI, F ; TASHJIAN, A. H</creatorcontrib><description>We have shown previously that overexpression of the ε isoform of protein kinase C (PKCε) in rat colonic epithelial cells causes malignant transformation, possibly by interacting with the ras signal transduction pathway (Oncogene 12: 847, 1996). We have now performed experiments to examine certain early steps in the ras signaling pathway. A marked increase of Raf-1 phosphorylation was detected in tumorigenic ras-transformed D/ras as well as in D/ε cells (overexpressing PKCε), compared to the nontumorigenic D/WT parental line. Moreover, in the PKCε-transformed D/ε cell line, stable transfection with a dominant-negative raf-1 (DNraf) sequence caused complete regression of the neoplastic phenotype. These results suggested that PKCε-induced transformation was associated with increased Raf-1 activation, and that DNraf could block the oncogenic effect of PKCε. Furthermore, transfection of D/WT cells with dominant-negative ras induced arrest of cell growth, and subsequent transfection with PKCε cDNA enhanced cell proliferation and induced neoplastic transformation. These results suggest that ras acts upstream of PKCε, and that overexpression of PKCε circumvents the block in cell proliferation caused by dominant-negative ras. 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source Nature Journals Online; EZB-FREE-00999 freely available EZB journals; SpringerLink Journals - AutoHoldings
subjects Biological and medical sciences
Cell growth
Cell physiology
Cell proliferation
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Colorectal cancer
Epithelial cells
Fundamental and applied biological sciences. Psychology
Genetic transformation
Kinases
Molecular and cellular biology
Phenotypes
Phosphorylation
Protein kinase C
Raf protein
Signal transduction
Transfection
title Protein kinase Cε is oncogenic in colon epithelial cells by interaction with the ras signal transduction pathway
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