Unknown

Dataset Information

0

Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation.


ABSTRACT: Oncogene-induced senescence is an important mechanism by which normal cells are restrained from malignant transformation. Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma. MYC inactivation was associated with prototypical markers of senescence, including acidic beta-gal staining, induction of p16INK4a, and p15INK4b expression. Moreover, MYC inactivation induced global changes in chromatin structure associated with the marked reduction of histone H4 acetylation and increased histone H3 K9 methylation. Osteosarcomas engineered to be deficient in p16INK4a or Rb exhibited impaired senescence and failed to exhibit sustained tumor regression upon MYC inactivation. Similarly, only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained tumor regression. The pharmacologic inhibition of signaling pathways implicated in oncogene-induced senescence including ATM/ATR and MAPK did not prevent senescence associated with MYC inactivation. Our results suggest that cellular senescence programs remain latently functional, even in established tumors, and can become reactivated, serving as a critical mechanism of oncogene addiction associated with MYC inactivation.

SUBMITTER: Wu CH 

PROVIDER: S-EPMC1941831 | biostudies-other | 2007 Aug

REPOSITORIES: biostudies-other

altmetric image

Publications

Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation.

Wu Chi-Hwa CH   van Riggelen Jan J   Yetil Alper A   Fan Alice C AC   Bachireddy Pavan P   Felsher Dean W DW  

Proceedings of the National Academy of Sciences of the United States of America 20070730 32


Oncogene-induced senescence is an important mechanism by which normal cells are restrained from malignant transformation. Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma. MYC inactivation was associated with prototypical markers of senescence, including acidic beta-gal staining, induction of p16INK4a, and p15INK4b expression. Moreover, MYC inactivation induced global  ...[more]

Similar Datasets

2012-09-06 | E-GEOD-40606 | biostudies-arrayexpress
| S-EPMC1637571 | biostudies-literature
2012-09-06 | GSE40606 | GEO
| S-EPMC7849765 | biostudies-literature
| S-EPMC7533841 | biostudies-literature
| S-EPMC196129 | biostudies-literature
| S-EPMC2991103 | biostudies-literature
| S-EPMC9475035 | biostudies-literature
| S-EPMC4414137 | biostudies-literature
| S-EPMC4851351 | biostudies-literature