Silencing of hdm2 oncogene by siRNA inhibits p53-dependent human breast cancer.
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.
Liu
Tie-gang
TG
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.
Yin
James Q
JQ
Shang
Bo-yang
BY
Min
Zhang
Z
He
Hong-wei
HW
Jiang
Jian-ming
JM
Chen
Fang
F
Zhen
Yong-su
YS
Shao
Rong-guang
RG
D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D017931:DNA Primers; D016147:Genes, Tumor Suppressor; D006801:Humans; D009857:Oncogenes; D034741:RNA, Small Interfering / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology
D017931:DNA Primers; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53