p21Waf1/Cip1 and p53 are downstream effectors of protein kinase C delta in tumor suppression and differentiation in human colon cancer cells

Gianpaolo Perletti, Emanuela Marras, Davide Dondi, Daniela Osti, Terenzio Congiu, Roberto Ferrarese, Magda De Eguileor, Armen H. Tashjian

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously demonstrated that the delta isoform of protein kinase C (PKCδ) is importantly involved in cell growth inhibition and tumor suppression in colon cancer cells. To investigate further the activity and mechanism of action of PKCδ, we have retrovirally transduced a PKCδ cDNA in HCT116 human colon cancer cells. PKCδ-overexpressing cells (HCT116/PKCδ) were growth-inhibited, showed marked morphologic changes and underwent multinucleation and phenotypic changes characteristic of mitotic catastrophe. Compared to controls, HCT116/PKCδ cells showed a highly attenuated tumorigenic profile and poor anchorage-independent growth. In addition, transfected cells established junction-coordinated intercellular communications, expressed cell surface microvilli and overexpressed the colon differentiation marker alkaline phosphatase. HCT116/PKCδ cells also produced the 89 kDa, carboxy-terminal catalytic domain of PARP. In HCT116/ PKCδ cells, p21Waf1/Cip1 and p53 were transiently upregulated for 48 hr after PKCδ transduction. In a p21 null subline of HCT116 cells (HCT116/p21null), overexpression of PKCδ did not affect tumorigenicity or differentiation, indicating that p21 is essential for the antitumorigenic activity of PKCδ. Similarly, overexpression of PKCδ caused no significant phenotypic changes in HCT116/E6 cells, an HCT116 subline in which the p53 protein is downregulated by the human papillomavirus E6 gene product. We conclude that overexpression of PKCδ in human colon cancer cells induces multiple antineoplastic effects that depend on the activities of p21 Waf1/CiP1 and p53.

Original languageEnglish
Pages (from-to)42-53
Number of pages12
JournalInternational Journal of Cancer
Volume113
Issue number1
DOIs
Publication statusPublished - Jan 1 2005

Keywords

  • Cell differentiation
  • p21
  • p53
  • PKC
  • Protein kinase C delta
  • Tumor suppression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'p21Waf1/Cip1 and p53 are downstream effectors of protein kinase C delta in tumor suppression and differentiation in human colon cancer cells'. Together they form a unique fingerprint.

Cite this