Overexpression of 14-3-3σ counteracts tumorigenicity by positively regulating p73 in vivo

Geng,Cuizhi; Sang,Meixiang; Yang,Ruiling; Gao,Wei; Zhou,Tao; Wang,Shijie

doi:10.3892/ol.2011.401

Overexpression of 14-3-3σ counteracts tumorigenicity by positively regulating p73 in vivo

Authors:
- Cuizhi Geng
- Meixiang Sang
- Ruiling Yang
- Wei Gao
- Tao Zhou
- Shijie Wang
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Affiliations: Breast Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Tumor Research Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Published online on: August 31, 2011 https://doi.org/10.3892/ol.2011.401
Pages: 1177-1182

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Abstract

14-3-3σ, one of the 14-3-3 family members, was initially identified as a human mammary epithelium-specific marker 1. The expression of 14-3-3σ is directly regulated by p53. It has been demonstrated that 14-3-3σ stabilizes p53 and enhances its transcriptional activity through the interaction with p53, suggesting that 14-3-3σ has a positive feedback effect on p53. Our previous study showed that 14-3-3σ is a direct transcriptional target of p73 and enhances the p73-mediated transcriptional as well as pro-apoptotic activity in vitro. In the present study, we explored the tumor-suppressive effect of 14-3-3σ by establishing a breast cancer xenograft nude mouse model with an inducible expression of 14-3-3σ or with an inducible expression of p53/p73 plus 14-3-3σ with ADR treatment. Tumor formation was then assayed. Moreover, 66 primary breast cancer specimens and paired tumor-free breast specimens obtained from the female patients were examined. Results showed that the expression of p73 and 14-3-3σ in breast cancer specimens was significantly lower than the tumor-free breast specimens and that 14-3-3σ expression was positively correlated with the expression of p73. Furthermore, overexpression of 14-3-3σ counteracts tumorigenicity by positively regulating p73 in p53-mutated or -deficient cancers in vivo. Therefore, our results may lead to the use of 14-3-3σ in the therapeutic application for the p53-mutated and p73-expressed breast cancer patients.

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