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: Toyokazu Sasaki, Koh-Ichi Nakashiro, Hiroshi Tanaka, Koji Azuma, Hiroyuki Goda, Shingo Hara, Jun Onodera, Ichiro Fujimoto, Nozomu Tanji, Masayoshi Yokoyama, Hiroyuki Hamakawa
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 399 Issue 1 Pg. 79-83 (Aug 13 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20638364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier Inc. All rights reserved.

Chemical References

• Protein Isoforms
• RNA, Small Interfering
• Proto-Oncogene Proteins c-akt

Topics

• Cell Line, Tumor
• Cell Proliferation
• Gene Knockdown Techniques
• Humans
• Male
• Prostatic Neoplasms (enzymology, therapy)
• Protein Isoforms (antagonists & inhibitors, genetics)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, genetics)
• RNA Interference
• RNA, Small Interfering (genetics)