Knockdown of Akt isoforms by RNA silencing suppresses the growth of human prostate cancer cells in vitro and in vivo |
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Authors: | Toyokazu Sasaki Hiroshi Tanaka Hiroyuki Goda Jun Onodera Nozomu Tanji Masayoshi Yokoyama |
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Affiliation: | a Department of Urology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan b Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime 791-0295, Japan c Department of Cell Growth and Tumor Regulation, Ehime University, Proteo-Medicine Research Center, 454 Shitsukawa, Toon, Ehime 791-0295, Japan d Koken Co., Ltd., 3-14-3 Mejiro, Toshima-ku, Tokyo 171-0031, Japan |
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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. |
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Keywords: | AR, androgen receptor BLAST, Basic Local Alignment Search Tool EDTA, ethylenediaminetetraacetic acid FBS, fetal bovine serum PI3K, phosphatidylinositol 3-kinase PTEN, phosphatase and tensin homolog deleted from chromosome 10 RNAi, RNA interference SD, standard deviation SDS, sodium dodecyl sulfate siGFP, siRNA specific for green fluorescent protein siRNA, small-interfering RNA |
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