Cytoplasmic expression of p21CIP1/WAF1 is correlated with IKKβ overexpression in human breast cancers

Bo Ping, Xianghuo He, Weiya Xia, Dung Fang Lee, Yongkun Wei, Dihua Yu, Gordon Mills, Daren Shi, Mien Chie Hung

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Regulation of cytoplasmic p21CIP/WAF1 (p21) is of great clinical significance in molecular oncology due to its identification as an antiapoptotic factor, a poor survival predictor as well as a drug-resistance inducer. A retrospective study of the immunohistochemical (IHC) profiles of 128 human primary breast cancers showed that increased total and cytoplasmic p21 expression were highly associated with the expression of IκB kinase β (IKKβ), the major catalytic subunit of the IKK complex and another crucial player in tumorigenesis and drug resistance. The causal relationship study based on cultured cell lines, MDA-MB-453 and MCF-7, confirmed that IKKβ overexpression did upregulate protein levels of total and cytoplasmic p21. Mechanistic investigation demonstrated that IKKβ increased p21 expression through upregulation of p21 mRNA level. Moreover, by Western blotting, IKKβ was found to be able to upregulate Akt phosphorylation on Ser 473. This novel finding indicated that IKKβ could mediate cytoplasmic p21 accumulation via activation of its downstream target Akt, which was known to phosphorylate p21 and lead to cytoplasmic localization of p21.

Original languageEnglish (US)
Pages (from-to)1103-1110
Number of pages8
JournalInternational Journal of Oncology
Volume29
Issue number5
DOIs
StatePublished - Nov 2006
Externally publishedYes

Keywords

  • Akt
  • Breast cancer
  • IKKβ
  • p21

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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