Abstract
Deregulated c-Myc expression leads to a cellular state where proliferation and apoptosis are equally favored depending on the cellular microenvironment. Since the apoptotic sensitivity of many cells is influenced by the status of the p53 tumor suppressor gene, we investigated whether the induction of apoptosis by DNA damage or non-genotoxic stress are also influenced by the p53 status of cells with altered c-Myc activity. Rat-1 fibroblasts expressing a conditional c-Myc allele (c-MycER), were transfected to express an antisense RNA complimentary to p53 mRNA. Expression of antisense p53 RNA decreased p53 protein levels and delayed p53 accumulation following c-Myc activation. Under hypoxic or low serum conditions, cells expressing antisense p53 were substantially more resistant to c-Myc-induced apoptosis than were control cells. c-Myc activation also sensitized Rat-1 cells to radiation-induced apoptosis. Rat-1 cells expressing antisense p53 RNA were more resistant to apoptosis induced by the combined effects of c-Myc activation and gamma irradiation. In a similar manner, apoptosis induced by c-Myc in serum starved, hypoxic or gamma irradiated fibroblasts was also inhibited by Bcl-2. These data indicate that p53 is involved in c-Myc-mediated apoptosis under a variety of stresses which may influence tumor growth, evolution and response to therapy.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Additional information
Edited by C.J. Thiele
Rights and permissions
About this article
Cite this article
Rupnow, B., Alarcon, R., Giaccia, A. et al. p53 mediates apoptosis induced by c-Myc activation in hypoxic or gamma irradiated fibroblasts. Cell Death Differ 5, 141–147 (1998). https://doi.org/10.1038/sj.cdd.4400328
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.cdd.4400328
Keywords
This article is cited by
-
The interplay between MYC and HIF in cancer
Nature Reviews Cancer (2008)
-
Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil
Cancer Chemotherapy and Pharmacology (2005)
-
ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth
Oncogene (2002)
-
c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells
Oncogene (2000)
-
Apoptosis-prone phenotype of human colon carcinoma cells with a high level amplification of the c-myc gene
Oncogene (1999)