Prostate-specific antitumor activity by probasin promoter-directed p202 expression.

Wen Y, Giri D, Yan DH, Spohn B, Zinner RG, Xia W, Thompson TC, Matusik RJ, Hung MC
Mol Carcinog. 2003 37 (3): 130-7

PMID: 12884364 · DOI:10.1002/mc.10129

p202, an interferon (IFN) inducible protein, arrests cell cycle at G1 phase leading to cell growth retardation. We previously showed that ectopic expression of p202 in human prostate cancer cells renders growth inhibition and suppression of transformation phenotype in vitro. In this report, we showed that prostate cancer cells with stable expression of p202 were less tumorigenic than the parental cells. The antitumor activity of p202 was further demonstrated by an ex vivo treatment of prostate cancer cells with p202 expression vector that showed significant tumor suppression in mouse xenograft model. Importantly, to achieve a prostate-specific antitumor effect by p202, we employed a prostate-specific probasin (ARR2PB) gene promoter to direct p202 expression (ARR2PB-p202) in an androgen receptor (AR)-positive manner. The ARR2PB-p202/liposome complex was systemically administered into mice bearing orthotopic AR-positive prostate tumors. We showed that parenteral administration of an ARR2PB-p202/liposome preparation led to prostate-specific p202 expression and tumor suppression in orthotopic prostate cancer xenograft model. Furthermore, with DNA array technique, we showed that the expression of p202 was accompanied by downregulation of G2/M phase cell-cycle regulators, cyclin B, and p55cdc. Together, our results suggest that p202 suppresses prostate tumor growth, and that a prostate-specific antitumor effect can be achieved by systemic administration of liposome-mediated delivery of ARR2PB-p202.

Copyright 2003 Wiley-Liss, Inc.

MeSH Terms (33)

Androgen-Binding Protein Animals Carrier Proteins Cdc20 Proteins Cell Cycle Proteins Cell Division Cell Transformation, Neoplastic Cyclin B Cyclin B1 Down-Regulation Gene Expression Gene Expression Profiling Genetic Therapy Humans Immunoenzyme Techniques Intracellular Signaling Peptides and Proteins Liposomes Male Mice Mice, Nude Neoplasms, Experimental Nuclear Proteins Phenotype Phosphoproteins Phosphorylation Promoter Regions, Genetic Prostatic Neoplasms Receptors, Androgen Retinoblastoma Protein Survival Rate Tumor Cells, Cultured Tumor Suppressor p53-Binding Protein 1 Xenograft Model Antitumor Assays

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