Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter.
The success of gene therapy using a RNA interference approach relies on small interfering RNA (siRNA) expression from a highly tissue-specific RNA polymerase II promoter rather than from ubiquitous RNA polymerase III. Accordingly, we have developed a prostate-specific vector that expresses siRNAs from the human prostate-specific antigen promoter, a RNA polymerase II promoter. Our data demonstrate androgen-dependent and tissue-specific siRNA-mediated gene silencing in the androgen-responsive prostate cancer cell line, LNCaP. The biological significance was evidenced by altered apoptotic activity through the inhibition of the apoptosis-related regulatory gene. These results demonstrate that siRNA-mediated gene silencing from a tissue-specific RNA polymerase II promoter could be a potential tool for tissue-specific gene therapy.
Song
Jun
J
Dental Research Institute, University of California Los Angeles (UCLA) School of Dentistry, UCLA, Los Angeles, California 90095, USA.
Pang
Shen
S
Lu
Yingchun
Y
Yokoyama
Kazunari K
KK
Zheng
Jun-Ying
JY
Chiu
Robert
R
D000728:Androgens / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D020868:Gene Silencing; D006801:Humans; D020287:In Situ Nick-End Labeling; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology
D000728:Androgens; D034741:RNA, Small Interfering; D048031:JNK Mitogen-Activated Protein Kinases; D017430:Prostate-Specific Antigen