Gene therapy approach in prostate cancer cells using an active Wnt signal.
BACKGROUND
Functional activation of beta-catenin/T-cell factor (Tcf) signaling plays an important role in the early events of carcinogenesis. In past recent years accumulated evidence has demonstrated a significant role for the Wnt pathway in the development and progression of human prostate cancer. The objective of the current study was to use a gene-targeting approach to selectively kill human prostate cancer cells with activated beta-catenin/Tcf signaling.


METHODS
A recombinant adenovirus that carries a lethal gene (PUMA) under the control of a beta-catenin/T-cell factor (Tcf)-responsive promoter (Ad-TOP-PUMA), was used to selectively target human prostate cancer cells (PC-3) in which the beta-catenin/Tcf pathway is activated, and compared its killing efficiency in cancer cells in which this pathway is inactive (DU145 cells). Ad-FOP-PUMA, carrying a mutant Tcf binding site, was used as a control virus. Cell viability was measured by methylene blue assay, and the level of beta-catenin/Tcf activity was measured by luciferase assay.


RESULTS
The Ad-TOP-PUMA adenovirus inhibited PC-3 cell growth in a dose and time-dependent fashion, but did not had any effect on DU145 cell growth.


CONCLUSIONS
Selective targeting of prostate cancer cells with the activated beta-catenin pathway may be a novel and effective therapy in prostate cancer.
Giladi
Nis
N
The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel.
Dvory-Sobol
Hadas
H
Sagiv
Eyal
E
Kazanov
Diana
D
Liberman
Eliezer
E
Arber
Nadir
N
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D018390:Gene Targeting; D005804:Genes, Lethal / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000737:chemistry; D008297:Male; D008751:Methylene Blue; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics* / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D008156:Luciferases; D008751:Methylene Blue