PMID- 9551622
OWN - NLM
STAT- MEDLINE
DCOM- 19980529
LR  - 20121115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 9
IP  - 5
DP  - 1998 Mar 20
TI  - Antisense c-myc retroviral vector suppresses established human prostate cancer.
PG  - 747-55
AB  - 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.
FAU - Steiner, M S
AU  - Steiner MS
AD  - Department of Urology, Vanderbilt University School of Medicine, Nashville, TN 
      37235, USA.
FAU - Anthony, C T
AU  - Anthony CT
FAU - Lu, Y
AU  - Lu Y
FAU - Holt, J T
AU  - Holt JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antisense Elements (Genetics))
RN  - EC 3.1.- (Ribonucleases)
SB  - IM
MH  - Animals
MH  - *Antisense Elements (Genetics)
MH  - Blotting, Southern
MH  - Blotting, Western
MH  - *Genes, myc
MH  - *Genetic Therapy
MH  - *Genetic Vectors
MH  - Humans
MH  - Male
MH  - Mammary Tumor Virus, Mouse/*genetics
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - Prostatic Neoplasms/pathology/*therapy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombination, Genetic
MH  - Ribonucleases
MH  - Tissue Distribution
MH  - Tumor Cells, Cultured
EDAT- 1998/04/29 00:00
MHDA- 1998/04/29 00:01
CRDT- 1998/04/29 00:00
PHST- 1998/04/29 00:00 [pubmed]
PHST- 1998/04/29 00:01 [medline]
PHST- 1998/04/29 00:00 [entrez]
AID - 10.1089/hum.1998.9.5-747 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1998 Mar 20;9(5):747-55. doi: 10.1089/hum.1998.9.5-747.