Cancer resistance in transgenic mice expressing the SAC module of Par-4

Yanming Zhao, Ravshan Burikhanov, Shirley Qiu, Subodh M. Lele, C. Darrell Jennings, Subbarao Bondada, Brett Spear, Vivek M. Rangnekar

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-κB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.

Original languageEnglish (US)
Pages (from-to)9276-9285
Number of pages10
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zhao, Y., Burikhanov, R., Qiu, S., Lele, S. M., Jennings, C. D., Bondada, S., Spear, B., & Rangnekar, V. M. (2007). Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Research, 67(19), 9276-9285. https://doi.org/10.1158/0008-5472.CAN-07-2124