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Research Articles: Therapeutics, Targets, and Development

Delivery of PTEN via a novel gene microcapsule sensitizes prostate cancer cells to irradiation

¹ Department Of Urology, Nara Medical University, Nara, Japan; ² Department Of Urology, Kinki University, Osaka-Sayama, Japan; ³ Department Of Biomaterials, Field Of Tissue Engineering, Kyoto University, Kyoto, Japan; and ⁴ Department Of Urology, University of Florida, Gainesville, Florida

Requests for reprints: Motoyoshi Tanaka, Department of Urology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan. Phone: 81-72-366-0221; Fax: 81-72-365-6273. E-mail: mtanaka{at}med.kindai.ac.jp

Abstract

The tumor suppressor gene MMAC/PTEN located on chromosome10q23.3 has dual phosphatase activity in the phosphoinositide-3-kinase signaling pathway and inhibits Akt activation, a serine-threonine kinase, which is involved in proliferative and antiapoptotic pathways. Furthermore, MMAC/PTEN is frequently inactivated in a variety of tumors including prostate cancer. In this study, we generated a new type of gene transfer drug, GelaTen, which is a microsphere of cationized gelatin hydrogels incorporating PTEN plasmid DNA. Using our previously reported radiation-resistant PC3-Bcl-2 human prostate cancer cells (PTEN deleted), we examined the efficacy of GelaTen to force the expression of PTEN in vivo to inhibit tumor growth after intratumoral injection alone or with irradiation. Combinational therapy with GelaTen and irradiation improved both the in vitro and in vivo efficacy of growth inhibition compared with GelaTen or irradiation alone. These data show that GelaTen gene therapy, enabling radiosensitization, can potentially treat prostate cancers that have MMAC/PTEN gene alterations associated with radioresistance. [Mol Cancer Ther 2008;7(7):1864–70]

Grant support: Ministry of Education, Sports, Science and Technology of Japan grant-in-aid 19591876 (M. Tanaka).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 10/16/07; revised 3/27/08; accepted 4/18/08.