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Deregulated E2F activity induces hyperplasia and senescence-like features in the mouse pituitary gland.


ABSTRACT: The retinoblastoma gene, RB1, is one of the most frequently mutated genes in human cancer. Rb heterozygous mice develop pituitary tumors with 100% incidence, and the E2F transcription factors are required for this. To assess whether deregulated E2F activity is sufficient to induce pituitary tumors, we generated transgenic mice expressing an inducible E2F3 protein in the intermediate lobe of the pituitary gland. We found that short-term deregulation of E2F activity, similar to the earliest stages of Rb loss, is able to induce abnormal proliferation of otherwise quiescent melanotrophs. However, while long-term exposure to deregulated E2F activity results in hyperplasia of the intermediate lobe, it did not lead to tumor formation. In fact, melanotrophs become insensitive to sustained E2F stim

SUBMITTER: Lazzerini Denchi E 

PROVIDER: S-EPMC1061636 | biostudies-literature | 2005 Apr

REPOSITORIES: biostudies-literature