title: Antisense c-myc retroviral vector suppresses established human prostate cancer.
abstract: Prostate cancer eventually becomes androgen resistant, resumes growth, and kills the patient. Characterization of genetic events that lead to androgen refractory prostatic neoplasia has revealed the frequent overexpression of c-myc and uncontrolled prostate cancer proliferation. A novel strategy to combat advanced prostate cancer utilized a replication incompetent retrovirus that contained the mouse mammary tumor virus (MMTV) promoter within the retroviral vector to allow transcription of antisense c-myc gene within target prostate tumor cells. The transduction of cultured DU145 cells by XM6:MMTV-antisense c-myc RNA retrovirus did not affect cell proliferation in culture, yet a single direct injection of MMTV-antisense c-myc viral media into established DU145 tumors in nude mice produced a 94.5% reduction in tumor size compared to tumors treated with control virus MTMV sense fos and untreated tumor by 70 days. Two animals in the antisense c-myc-treated group had complete regression of their tumors. Histopathological examination of the tumors revealed that MMTV-antisense c-myc-transduced DU145 tumors had increased tumor cell differentiation, decreased invasion, and a marked stromal response. The mechanism for the antitumor effect of MMTV-antisense c-myc retrovirus appears to be suppression of c-myc mRNA and protein, and decreased bcl-2 protein. The in vivo transduction of prostate cancer cells with MMTV-antisense c-myc retroviruses reduced tumor growth by suppressing c-myc, resulting in the down-regulation of bcl-2 protein. Consequently, the MMTV-antisense c-myc retrovirus may be useful for gene therapy against advanced, hormone-refractory prostate cancer.
authors.affiliation: Department of Urology, Vanderbilt University School of Medicine, Nashville, TN 37235, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Steiner
authors.forename: C T
authors.initials: CT
authors.lastname: Anthony
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: J T
authors.initials: JT
authors.lastname: Holt
mesh_terms: D000818:Animals; D016375:Antisense Elements (Genetics); D015139:Blotting, Southern; D015153:Blotting, Western; D016259:Genes, myc; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic; D012260:Ribonucleases; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D016375:Antisense Elements (Genetics); D012260:Ribonucleases