p27 deficiency cooperates with Bcl-2 but not Bax to promote T-cell lymphoma.

Autor: Ningli Cheng, Christopher I van de Wetering, C Michael Knudson
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Zdroj: PLoS ONE, Vol 3, Iss 4, p e1911 (2008)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0001911
Popis: The effect of Bcl-2 on oncogenesis is complex and expression may either delay or accelerate oncogenesis. The pro-oncogenic activity is attributed to its well characterized anti-apoptotic function while the anti-oncogenic function has been attributed to its inhibition of cellular proliferation. Recent studies demonstrate that p27 may mediate the effects of Bcl-2 on cellular proliferation. We hypothesized that p27 may suppress tumor formation by Bcl-2 family members. To test this hypothesis, cell cycle inhibition and lymphoma development were examined in Lck-Bcl-2 and Lck-Bax38/1 transgenic mice deficient in p27. Strikingly, p27 deficiency synergistically cooperates with Bcl-2 to increase T cell hyperplasia and development of spontaneous T cell lymphomas. Within 1 year, >90% of these mice had developed thymic T cell lymphomas. This high penetrance contrasts with a one year incidence of
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