title: Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Urology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Sasaki
authors.forename: Koh-Ichi
authors.initials: K
authors.lastname: Nakashiro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Koji
authors.initials: K
authors.lastname: Azuma
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Goda
authors.forename: Shingo
authors.initials: S
authors.lastname: Hara
authors.forename: Jun
authors.initials: J
authors.lastname: Onodera
authors.forename: Ichiro
authors.initials: I
authors.lastname: Fujimoto
authors.forename: Nozomu
authors.initials: N
authors.lastname: Tanji
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hamakawa
mesh_terms: 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
chemical_list: D020033:Protein Isoforms; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt