p53 regulates Stat3 phosphorylation and DNA binding activity in human prostate cancer cells expressing constitutively active Stat3

Jiayuh Lin, Huaijing Tang, Xiaohong Jin, Guiyue Jia, Jer Tsong Hsieh

Research output: Contribution to journalArticle

75 Scopus citations

Abstract

Constitutive activation of the signal transducer and activator of transcription 3 (Stat3) and mutation of the p53 are both commonly detected in human prostate cancer cells. We sought to investigate whether there is functional regulation of Stat3 by wild-type (wt) p53. Our results demonstrate that expression of wt p53 but not mutant p53 significantly reduced tyrosine phosphorylation of Stat3 and inhibited Stat3 DNA binding activity in both DU145 and Tsu prostate cancer cell lines that express constitutively active Stat3. Expression of the p53 downstream target, p21WAF-1, did not have any inhibitory effect on Stat3 phosphorylation. Wt p53 but not p21WAF-1 induced dramatic apoptosis in these prostate cancer cells. Expression of wt p53 did not cause a reduction of phosphorylation-independent Stat3 protein and reduction of phosphorylation of three unrelated protein kinases, ERK1, ERK2 (ERK1/2), and AKT. Interestingly, p53-dependent apoptosis occurred in the presence of high levels of phosphorylated AKT and ERK1/2 in both DU145 and Tsu prostate cancer cells. Further, we evaluated a series of established human prostate, breast, and ovarian cancer cell lines and found that all cancer cell lines expressing constitutively active Stat3, only harbor mutated or deleted p53. One implication of these results is that the anti-proliferative activities of p53 may not be compatible with the constitutive Stat3 signal in cancer cells.

Original languageEnglish (US)
Pages (from-to)3082-3088
Number of pages7
JournalOncogene
Volume21
Issue number19
DOIs
StatePublished - Jan 1 2002

Keywords

  • Apoptosis
  • p53
  • Prostate cancer
  • Stat3

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'p53 regulates Stat3 phosphorylation and DNA binding activity in human prostate cancer cells expressing constitutively active Stat3'. Together they form a unique fingerprint.

  • Cite this