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
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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.