REGULATION OF RADIATION-INDUCED APOPTOSIS IN ONCOGENE-TRANSFECTED FIBROBLASTS - INFLUENCE OF H-RAS ON THE G2 DELAY

Citation
Wg. Mckenna et al., REGULATION OF RADIATION-INDUCED APOPTOSIS IN ONCOGENE-TRANSFECTED FIBROBLASTS - INFLUENCE OF H-RAS ON THE G2 DELAY, Oncogene, 12(2), 1996, pp. 237-245
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,Biology,"Cell Biology
Journal title
ISSN journal
0950-9232
Volume
12
Issue
2
Year of publication
1996
Pages
237 - 245
Database
ISI
SICI code
0950-9232(1996)12:2<237:RORAIO>2.0.ZU;2-0
Abstract
Primary fibroblasts, after serum withdrawal or after irradiation, do n ot undergo apoptosis. Myc-transfected fibroblasts, in contrast, underg o apoptosis upon serum withdrawal and after irradiation. We have studi ed the relationship of apoptosis induction to effects on the G2 phase cell cycle in a series of rat embryo cells transformed by ras(H) plus myc or immortalized by myc alone. In this system, while the presence o f ras(H) had little effect on the extent of apoptosis induction by ser um withdrawal, ras(H) greatly suppressed the apoptotic response of myc -transfected cells to X-rays. The cells into which ras(H) had been int roduced showed a profound G2 arrest associated with suppression of cyc lin B1 mRNA expression. In contrast, cells with myc alone had a minima l G2 delay after irradiation and no suppression of cyclin B1 mRNA expr ession, We hypothesize that ras(H), by influencing the G2 response of cells to X-rays, exerts an anti-apoptotic effect. In support of this h ypothesis; we found that treatment of cells with caffeine, an agent th at relieves the G2 delay after irradiation resulted in increased apopt osis in the irradiated cells, but not in control cells.