Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells

作者: Qingxia Zhao , Ming Zhao , Amanda B. Parris , Ying Xing , Xiaohe Yang

DOI: 10.3892/IJO.2016.3588

关键词:

摘要: Genistein is a soy isoflavone with phytoestrogen and tyrosine kinase inhibitory properties. High intake of soy/genistein has been associated reduced breast cancer risk. Despite the advances in genistein-mediated antitumor studies, underlying mechanisms remain unclear. In present study, we investigated genistein-induced regulation cancerous inhibitor protein phosphatase 2A (CIP2A), novel oncogene frequently overexpressed cancer, its functional impact on growth inhibition apoptosis. We demonstrated that genistein induced downregulation CIP2A MCF-7-C3 T47D cells, which was correlated apoptotic activities. Overexpression attenuated, whereas knockdown sensitized, further showed involved both transcriptional suppression proteasomal degradation. particular, at higher concentrations concurrent E2F1 CIP2A. attenuated mRNA, indicating role Taken together, our results identified as target modulation E2F1-mediated contributes to downregulation. These data advance understanding apoptosis, support investigation therapeutic relevant anticancer agents.

参考文章(52)
Paula González-Alonso, Ion Cristóbal, Rebeca Manso, Juan Madoz-Gúrpide, Jesús García-Foncillas, Federico Rojo, PP2A inhibition as a novel therapeutic target in castration-resistant prostate cancer Tumor Biology. ,vol. 36, pp. 5753- 5755 ,(2015) , 10.1007/S13277-015-3849-5
Fazlul H. Sarkar, Yiwei Li, Mechanisms of cancer chemoprevention by soy isoflavone genistein. Cancer and Metastasis Reviews. ,vol. 21, pp. 265- 280 ,(2002) , 10.1023/A:1021210910821
Weifang Zhang, Hanxiang Chen, Yan Chen, Juan Liu, Xiao Wang, Xiuping Yu, Jason J. Chen, Weiming Zhao, Cancerous inhibitor of protein phosphatase 2A contributes to human papillomavirus oncoprotein E7-induced cell proliferation via E2F1. Oncotarget. ,vol. 6, pp. 5253- 5262 ,(2015) , 10.18632/ONCOTARGET.2867
T. Akiyama, J. Ishida, S. Nakagawa, H. Ogawara, S. Watanabe, N. Itoh, M. Shibuya, Y. Fukami, Genistein, a specific inhibitor of tyrosine-specific protein kinases. Journal of Biological Chemistry. ,vol. 262, pp. 5592- 5595 ,(1987) , 10.1016/S0021-9258(18)45614-1
Anchit Khanna, John E. Pimanda, Clinical significance of cancerous inhibitor of protein phosphatase 2A in human cancers International Journal of Cancer. ,vol. 138, pp. 525- 532 ,(2016) , 10.1002/IJC.29431
Jacques Ferlay, Isabelle Soerjomataram, Rajesh Dikshit, Sultan Eser, Colin Mathers, Marise Rebelo, Donald Maxwell Parkin, David Forman, Freddie Bray, Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer. ,vol. 136, ,(2015) , 10.1002/IJC.29210
Pradip De, Jennifer Carlson, Brian Leyland-Jones, Nandini Dey, Oncogenic nexus of cancerous inhibitor of protein phosphatase 2A (CIP2A): an oncoprotein with many hands. Oncotarget. ,vol. 5, pp. 4581- 4602 ,(2014) , 10.18632/ONCOTARGET.2127
Juandong Wang, Tao Huang, Jianzhi Sun, Yuan Yu, Zhifang Liu, Wenjuan Li, Jihui Jia, Chunyan Chen, CIP2A is overexpressed and involved in the pathogenesis of chronic myelocytic leukemia by interacting with breakpoint cluster region-Abelson leukemia virus. Medical Oncology. ,vol. 31, pp. 112- ,(2014) , 10.1007/S12032-014-0112-7
Guangzhe Yu, Guohong Liu, Juan Dong, Yingyu Jin, Clinical implications of CIP2A protein expression in breast cancer. Medical Oncology. ,vol. 30, pp. 524- ,(2013) , 10.1007/S12032-013-0524-9
Teruki Oki, Yoshihiro Sowa, Tohru Hirose, Nobumasa Takagaki, Mano Horinaka, Ryoko Nakanishi, Chikako Yasuda, Tatsushi Yoshida, Motohiro Kanazawa, Yoshiko Satomi, Hoyoku Nishino, Tsuneharu Miki, Toshiyuki Sakai, Genistein induces Gadd45 gene and G2/M cell cycle arrest in the DU145 human prostate cancer cell line. FEBS Letters. ,vol. 577, pp. 55- 59 ,(2004) , 10.1016/J.FEBSLET.2004.09.085