Gene therapy approach in prostate cancer cells using an active Wnt signal.

Abstract

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.

• Authors: Nis Giladi, Hadas Dvory-Sobol, Eyal Sagiv, Diana Kazanov, Eliezer Liberman, Nadir Arber
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 61 Issue 9 Pg. 527-30 (Oct 2007) ISSN: 0753-3322 [Print] France
• PMID: 17904788 (Publication Type: Journal Article)

Chemical References

• Apoptosis Regulatory Proteins
• BBC3 protein, human
• Proto-Oncogene Proteins
• TCF Transcription Factors
• Wnt Proteins
• beta Catenin
• Luciferases
• Methylene Blue

Topics

• Adenoviridae (genetics)
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins (genetics)
• Cell Line, Tumor
• Cell Survival
• Gene Targeting
• Genes, Lethal (genetics)
• Genetic Therapy
• Genetic Vectors
• Humans
• Luciferases (chemistry)
• Male
• Methylene Blue
• Plasmids (genetics)
• Prostatic Neoplasms (genetics, therapy)
• Proto-Oncogene Proteins (genetics)
• Signal Transduction (physiology)
• TCF Transcription Factors (genetics)
• Up-Regulation (genetics)
• Wnt Proteins (genetics, physiology)
• beta Catenin (genetics)