Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo.
The serine/threonine kinase Akt has three highly homologous isoforms in mammals: Akt1, Akt2, and Akt3. Recent studies indicate that Akt is often constitutively active in many types of human malignancy. Here we investigated the expression and function of Akt isoforms in human prostatic carcinoma cells. Initially, we used Western blotting to examine Akt expression in four human prostate cancer cell lines. Next, small-interfering RNAs (siRNAs) specific for Akt isoforms were used to elucidate their role on the in vitro and in vivo growth of prostate cancer cells. Expression of Akt1 and Akt2 was detected in all cells tested, but Akt3 was expressed only in cancer cells that did not express androgen receptors. All synthetic siRNAs against Akt isoforms suppressed their expression and inhibited the growth of cancer cells in vitro. Furthermore, atelocollagen-mediated systemic administration of siRNAs significantly reduced the growth of tumors that had been subcutaneously xenografted. These results suggest that targeting Akt isoforms could be an effective treatment for prostate cancers.
Sasaki
Toyokazu
T
Department of Urology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
Nakashiro
Koh-Ichi
K
Tanaka
Hiroshi
H
Azuma
Koji
K
Goda
Hiroyuki
H
Hara
Shingo
S
Onodera
Jun
J
Fujimoto
Ichiro
I
Tanji
Nozomu
N
Yokoyama
Masayoshi
M
Hamakawa
Hiroyuki
H
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000628:therapy*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D020033:Protein Isoforms; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt