Alcohol consumption and decreased risk of non-Hodgkin lymphoma: role of mTOR dysfunction

作者：Hagner Patrick R; Mazan Mamczarz Krystyna; Dai Bojie; Corl Sharon; Zhao X Frank; Gartenhaus Ronald B^*

来源：Blood, 2009, 113(22): 5526-5535.

DOI：10.1182/blood-2008-11-191783

Several epidemiologic studies support the emerging paradigm that current alcohol consumers have decreased risk of most types of non-Hodgkin lymphoma. The observed lower risk among people who drank alcohol does not seem to vary with beverage type. The mechanisms accounting for alcohol-induced decrease in the incidence of lymphomas remain largely unknown. We demonstrate that low-dose chronic exposure to ethanol inhibits mammalian target of rapamycin (mTOR) C1 complex formation, resulting in decreased phosphorylation events involved in mTOR pathway signaling in a lymphoid-tissue specific manner. These changes in mTOR signaling lead to a decrease in eIF4E associated with the translation initiation complex and a repression of global cap-dependent synthesis in both lymphoma cell lines and normal donor lymphocytes. We show that chronic exposure of ethanol at physiologically relevant concentrations in a xenograft model results in a striking inhibition of lymphoma growth. Our data support a paradigm in which chronic ethanol exposure inhibits mTOR signaling in lymphocytes with a significant repression of cap-dependent translation, reducing the tumorigenic capacity of non-Hodgkin lymphoma in a human xenograft model. The ethanol-mediated repression of mTOR signaling coupled with decreased in vivo lymphoma growth underscore the critical role of mTOR signaling and translation in lymphoma. (Blood. 2009; 113: 5526-5535)

• 出版日期2009-5-28