Regulation of PTEN expression in intestinal epithelial cells by c-Jun NH2-terminal kinase activation and nuclear factor-κB inhibition

Qingding Wang, Yuning Zhou, Xiaofu Wang, Dai H. Chung, B. Mark Evers

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The tumor suppressor protein phosphatase and tensin homologue deleted on chromosome ten (PTEN) plays an important role in intestinal cell proliferation and differentiation and tumor suppression by antagonizing phosphatidylinositol 3-kinase. Despite its importance,the molecular mechanisms regulating PTEN expression are largely undefined. Here, we show that treatment of the colon cancer cell line HT29 with the differentiating agent sodium butyrate (NaBT) increased PTEN protein and mRNA expression and induced c-Jun NH 2-terminal kinase (JNK) activation. Inhibition of JNK by chemical or genetic methods attenuated NaBT-induced PTEN expression. In addition,our findings showed a cross-talk between nuclear factor κB (NF-κB) and JNK with respect to PTEN regulation. Overexpression of the NF-κB superrepressor increased PTEN expression and JNK activity, whereas overexpression of the p65 NF-κB subunit reduced both basal and NaBT-mediated JNK activation and PTEN expression. Moreover, we showed that overexpression of PTEN or treatment with NaBT increased expression of the cyclin-dependent kinase inhibitor p27kip1 in HT29 cells; this induction was attenuated by inhibition of PTEN or JNK expression or overexpression of p65. Finally, we show a role for PTEN in NaBT-mediated cell death and differentiation. Our findings suggest that the JNK/PTEN and NF-κB/PTEN pathways play a critical role in normal intestinal homeostasis and colon carcinogenesis.

Original languageEnglish (US)
Pages (from-to)7773-7781
Number of pages9
JournalCancer Research
Volume67
Issue number16
DOIs
StatePublished - Aug 15 2007
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Phosphotransferases
Epithelial Cells
Cell Differentiation
PTEN Phosphohydrolase
Phosphatidylinositol 3-Kinase
Tumor Suppressor Proteins
HT29 Cells
Butyric Acid
Cyclin-Dependent Kinases
Phosphoprotein Phosphatases
Colonic Neoplasms
Colon
Carcinogenesis
Homeostasis
Cell Death
Chromosomes
Cell Proliferation
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Regulation of PTEN expression in intestinal epithelial cells by c-Jun NH2-terminal kinase activation and nuclear factor-κB inhibition. / Wang, Qingding; Zhou, Yuning; Wang, Xiaofu; Chung, Dai H.; Evers, B. Mark.

In: Cancer Research, Vol. 67, No. 16, 15.08.2007, p. 7773-7781.

Research output: Contribution to journalArticle

Wang, Qingding ; Zhou, Yuning ; Wang, Xiaofu ; Chung, Dai H. ; Evers, B. Mark. / Regulation of PTEN expression in intestinal epithelial cells by c-Jun NH2-terminal kinase activation and nuclear factor-κB inhibition. In: Cancer Research. 2007 ; Vol. 67, No. 16. pp. 7773-7781.
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