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. 2004 Nov;11(11):748-56.
doi: 10.1038/sj.cgt.7700753.

Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer

Tie-gang Liu  1 , James Q Yin, Bo-yang Shang, Zhang Min, Hong-wei He, Jian-ming Jiang, Fang Chen, Yong-su Zhen, Rong-guang Shao
Affiliations

Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer

Tie-gang Liu et al. Cancer Gene Ther. 2004 Nov.

Abstract

RNA interference technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Here our results showed that hdm2-siRNA silenced its target mRNA specifically and effectively in human breast cancer cells, reduced tumor cell proliferation and induced apoptotic cell death. Other molecular features modified by hdm2-siRNA included decreased Bcl-2, NF-kappaB, survivin, Ras and Raf levels, elevated p53, p21, BRCA1, Bax, and caspase levels as well as altered expression of other genes. hdm2-siRNA also caused cell cycle arrest at G1 phases with reduction in cyclin and Cdk proteins. In addition, hdm2-siRNA displayed in vivo antitumor activity and increased therapeutic effectiveness of mitomycin in MCF-7 xenografts. Thus, hdm2-siRNA may be a promising gene-specific drug for the treatment of human breast cancer and other tumors.

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