Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis

Xiaoyun Cheng, Weiya Xia, Jer Yen Yang, Jennifer L. Hsu, Chao Kai Chou, Hui Lung Sun, Shannon L. Wyszomierski, Gordon B. Mills, William J. Muller, Dihua Yu, Mien Chie Hung

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

While p21 is well known to inhibit cyclin-CDK activity in the nucleus and it has also been demonstrated to have oncogenic properties in different types of human cancers. In vitro studies showed that the oncogenic function of p21is closely related to its cytoplasmic localization. However, it is unclear whether cytoplasmic p21 contributes to tumorigenesis in vivo. To address this question, we generated transgenic mice expressing the Akt-phosphorylated form of p21 (p21T145D) in the mammary epithelium. The results showed that Akt-activated p21 was expressed in the cytoplasm of mammary epithelium. Overexpression of Akt-activated p21 accelerated tumor onset and promoted lung metastasis in MMTV/. neu mice, providing evidence that p21, especially cytoplasmic phosphorylated p21, has an oncogenic role in promoting mammary tumorigenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)103-107
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume403
Issue number1
DOIs
StatePublished - Dec 3 2010
Externally publishedYes

Keywords

  • Lung metastasis
  • Mammary tumorigenesis
  • P21
  • PKB/Akt

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Cheng, X., Xia, W., Yang, J. Y., Hsu, J. L., Chou, C. K., Sun, H. L., Wyszomierski, S. L., Mills, G. B., Muller, W. J., Yu, D., & Hung, M. C. (2010). Activation of p21(CIP1/WAF1) in mammary epithelium accelerates mammary tumorigenesis and promotes lung metastasis. Biochemical and Biophysical Research Communications, 403(1), 103-107. https://doi.org/10.1016/j.bbrc.2010.10.126