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Prostate‐specific antitumor activity by probasin promoter‐directed p202 expression
Author(s) -
Wen Yong,
Giri Dipak,
Yan DuenHwa,
Spohn Bill,
Zinner Ralph G.,
Xia Weiya,
Thompson Timothy C.,
Matusik Robert J.,
Hung MienChie
Publication year - 2003
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.10129
Subject(s) - prostate cancer , cancer research , biology , prostate , ectopic expression , cell cycle , microbiology and biotechnology , cell , cancer , cell culture , biochemistry , genetics
p202, an interferon (IFN) inducible protein, arrests cell cycle at G 1 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 (ARR 2 PB) gene promoter to direct p202 expression (ARR 2 PB‐p202) in an androgen receptor (AR)–positive manner. The ARR 2 PB‐p202/liposome complex was systemically administered into mice bearing orthotopic AR‐positive prostate tumors. We showed that parenteral administration of an ARR 2 PB‐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 G 2 /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 ARR 2 PB‐p202. © 2003 Wiley‐Liss, Inc.