Gene therapy of prostate xenograft tumors with a p75NTR lipoplex.
The p75neurotrophin receptor (p75NTR) has been characterized as a tumor suppressor in human prostate cancer. Ectopic re-expression of this cell surface receptor protein in prostate cancer cell lines has been shown to increase the frequency of apoptosis and concurrently reduce the rate of cellular proliferation. Since it is difficult to maintain a therapeutic level of this membrane receptor protein by systemic administration in the blood, we utilized an alternative gene therapy strategy based upon intra-tumoral injection into xenografts of PC-3 prostate tumor cells of a lipoplex containing the p75NTR gene. Administration of the p75NTR gene into subcutaneous PC-3 xenografts suppressed in a dose-dependent manner the growth of tumors. Within the gene therapy-treated tumors, re-expression of the p75NTR gene product was associated with increased apoptosis and reduced proliferation of tumor cells. These results suggest that the p75NTR may be a suitable candidate for gene therapy of prostate cancer cells.
Allen
Jeffrey
J
Department of Cell Biology, Georgetown University Medical Center, Washington DC, USA.
Khwaja
Fatima
F
Djakiew
Daniel
D
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
D008081:Liposomes; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D004247:DNA