PMID- 8886839
OWN - NLM
STAT- MEDLINE
DCOM- 19970122
LR  - 20121115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 7
IP  - 14
DP  - 1996 Sep 10
TI  - Molecular therapy with recombinant p53 adenovirus in an androgen-independent, 
      metastatic human prostate cancer model.
PG  - 1683-91
AB  - The lethal phenotypes of advanced prostate cancer are androgen independent (AI) 
      and metastatic to the axial skeleton. Our laboratory has developed an AI mouse 
      model of metastatic human prostate cancer. In this communication, we report the 
      development of tumor suppressor gene therapy in this AI and metastatic (C4-2) 
      cancer model. By using recombinant adenovirus as a delivery vehicle, we 
      introduced a wild-type p53 tumor suppressor gene into prostate cancer cell lines. 
      Despite a silent mutation at codon 152 of the p53 gene, C4-2 cells express 
      functional, but low, levels of p53 protein. However, the other prostatic cell 
      lines, PC-3 and DU145, have a deletion mutation and two point mutations of the 
      p53 gene, respectively. In vitro studies showed that cell growth, as measured by 
      the thymidine incorporation assay, was inhibited in the C4-2, PC-3, and DU145 
      cells infected with wild-type p53 adenovirus in comparison to control viruses. 
      Recombinant wild-type p53 adenovirus inhibited prostate tumor growth and its 
      production of prostate-specific antigen (PSA) when injected into C4-2 tumors in 
      nude mice. All p53-treated mice were tumor free as long as 12 weeks after 
      cessation of the 8-week treatment regimen. Two of 8 p53-treated mice developed 
      small tumors growing at distant sites after a prolonged period of follow-up 
      observation. Moreover, other AI prostate cancer cells, PC-3 and DU145, treated 
      with Ad5-CMV-p53 failed to develop into tumors in vivo. This gene therapy 
      strategy may be used against AI prostatic cancer regardless of p53 gene mutation 
      status.
FAU - Ko, S C
AU  - Ko SC
AD  - Urology Research Laboratory, University of Texas M.D. Anderson Cancer Center, 
      Houston 77030, USA.
FAU - Gotoh, A
AU  - Gotoh A
FAU - Thalmann, G N
AU  - Thalmann GN
FAU - Zhau, H E
AU  - Zhau HE
FAU - Johnston, D A
AU  - Johnston DA
FAU - Zhang, W W
AU  - Zhang WW
FAU - Kao, C
AU  - Kao C
FAU - Chung, L W
AU  - Chung LW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Androgens)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Adenoviruses, Human/*genetics
MH  - Androgens/physiology
MH  - Animals
MH  - Cell Division
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Transfer Techniques
MH  - Genes, p53/*genetics
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Mutation
MH  - Neoplasm Metastasis
MH  - Prostate-Specific Antigen/blood
MH  - Prostatic Neoplasms/pathology/*therapy
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/analysis
EDAT- 1996/09/10 00:00
MHDA- 1996/09/10 00:01
CRDT- 1996/09/10 00:00
PHST- 1996/09/10 00:00 [pubmed]
PHST- 1996/09/10 00:01 [medline]
PHST- 1996/09/10 00:00 [entrez]
AID - 10.1089/hum.1996.7.14-1683 [doi]
PST - ppublish
SO  - Hum Gene Ther. 1996 Sep 10;7(14):1683-91. doi: 10.1089/hum.1996.7.14-1683.