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Prostate‐tumor targeting of gene expression by lentiviral vectors containing elements of the probasin promoter
Author(s) -
Yu Duan,
Jia William W.,
Gleave Martin E.,
Nelson Colleen C.,
Rennie Paul S.
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20010
Subject(s) - lncap , du145 , prostate cancer , viral vector , cancer research , biology , microbiology and biotechnology , green fluorescent protein , reporter gene , transfection , genetic enhancement , hela , cell culture , gene expression , gene , cancer , biochemistry , genetics , recombinant dna
BACKGROUND Lentiviruses are retroviruses that can infect and stably integrate into the chromatin of non‐dividing cells. The purpose of this study was to determine whether lentiviral vectors containing the probasin (PB) promoter displayed prostate‐specific, androgen‐regulated, and persistent gene expression. METHODS Three lentiviral‐PB promoter/enhanced green fluorescent protein (EGFP)‐reporter vectors together with a control lentiviral‐CMV‐EGFP, were tested by microscopy and flowcytometry for expression of EGFP after infection of human prostate cancer cells (LNCaP, PC‐3, PC‐3(hAR), and Du145 cells) and non‐prostate cells (COS‐1, HeLa, HeLa(hAR), and MCF‐7 cells). RESULTS All cells infected in vitro with lentiviral‐CMV vectors expressed EGFP, whereas with lentiviral‐PB vectors (the most potent being Lv‐ARR 2 PB), reporter expression was only observed in LNCaP cells with a small amount seen in androgen‐independent PC‐3 cells. Stable or transient transfection of androgen receptor only raised EGFP expression in prostate‐derived cell lines, but did not change tumor specificity. With Lv‐ARR 2 PB infected LNCaP cells, androgens regulated EGFP both in vitro and in vivo. After intra‐tumor injection of this vector, EGFP expression was observed in LNCaP tumors, but not in A‐549 lung or CaKi‐2 kidney tumors. CONCLUSIONS Lv‐ARR 2 PB may be an ideal vector for prostate‐tumor targeting and for persistent, hormone‐enhanced expression of a therapeutic gene to treat slow growing prostate tumors. © 2004 Wiley‐Liss, Inc.