Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ

Citation
Tj. Wang et al., Comparisons of tumor suppressor p53, p21, and p16 gene therapy effects on glioblastoma tumorigenicity in situ, BIOC BIOP R, 287(1), 2001, pp. 173-180
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
287
Issue
1
Year of publication
2001
Pages
173 - 180
Database
ISI
SICI code
0006-291X(20010914)287:1<173:COTSPP>2.0.ZU;2-Y
Abstract
The mutation and/or deletion of tumor suppressor genes have been postulated to play a major role in the genesis and the progression of gliomas. In thi s study, the functional expression and efficacy in tumor suppression of 3 t umor suppressor genes (p53, p21, and p16) were tested and compared in a rat GBM cell line (RT-2) after retrovirus mediated gene delivery in vitro and in vivo. Significant reductions in tumor cell growth rate were found in p16 and p21 infected cells (60 +/- 12% vs 66 +/- 15%) compared to p53 (35 +/- 9%). In vitro colony formation assay also showed significant reductions aft er p16 and p21 gene delivery (98 +/- 5% vs 91 +/- 10%) compared to p53 (50 +/- 18%). In addition, the tumor suppression efficacy were investigated and compared in vivo. Retroviral mediated p16 and p21 gene deliveries in gliob lastomas resulted in more than 90% reductions in tu mor growth (92 +/- 26% vs 90 +/- 22%) compared to p53 (62 +/- 18%). Tumor suppressor gene insertio ns in situ further prolonged animal survival. Overall p16 and p21 genes sho wed more powerful tumor suppressor effects than p53. The results were not s urprising, as p16 and p21 are more downstream in the cell cycle regulatory pathway compared to p53. Moreover, the mechanism involved in each of their suppressor effects is different. This study demonstrates the feasibility of using tumor suppressor genes in regulating the growth of glioma in vitro a nd in situ. (C) 2001 Academic Press.