A p53/ARF-dependent anticancer barrier activates senescence and blocks tumorigenesis without impacting apoptosis.

ABSTRACT:

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In response to oncogene activation and oncogene-induced aberrant proliferation, mammalian cells activate apoptosis and senescence, usually via the p53-ARF tumor-suppressor pathway. Apoptosis is a known barrier to cancer and is usually downregulated before full malignancy, but senescence as an anticancer barrier is controversial due to its presence in the tumor environment. In addition, senescence may aid cancer progression via releasing senescence-associated factors that instigate neighboring tumor cells. Here, it is demonstrated that apoptosis unexpectedly remains robust in ErbB2 (ERBB2/HER2)-initiated mammary early lesions arising in adult mice null for either p53 or ARF. These early lesions, however, downregulate senescence significantly. This diminished senescence re

SUBMITTER: Sinha VC 

PROVIDER: S-EPMC4336810 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature