Bfl-1 is a crucial pro-survival nuclear factor-κB target gene in Hodgkin/Reed-Sternberg cells.

Autor: Loughran ST; School of Biotechnology and National Centre for Sensor Research, Dublin City University, Dublin 9, Ireland., Campion EM, D'Souza BN, Smith SM, Vrzalikova K, Wen K, Murray PG, Walls D
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2011 Dec 15; Vol. 129 (12), pp. 2787-96. Date of Electronic Publication: 2011 Apr 13.
DOI: 10.1002/ijc.25950
Abstrakt: Hodgkin/Reed-Sternberg (H/RS) cells are believed to represent clonal progeny of Germinal Centre B cells that have escaped negative selection by evading apoptosis. Aberrant constitutive activity of the transcription factor NF-κB plays a key role in the pathogenesis of Hodgkin's Lymphoma (HL), conferring a survival advantage on H/RS cells. Bfl-1 is a pro-survival NF-κB target gene from the Bcl-2 family of apoptosis-regulating proteins. Here, we report that bfl-1 (also known as A1 or GRS) is frequently expressed in primary H/RS cells from HL tumor biopsies and that elevated bfl-1 expression is a feature of H/RS derived cell lines. We show that bfl-1 is an NF-κB target gene in this cell context and that this regulation is effected through a p65-binding DNA element located in its promoter. We demonstrate that ectopic Bfl-1 can rescue cultured H/RS cells from apoptosis induced by pharmacological inhibitors of NF-κB, and that knockdown of bfl-1 potentiates the pro-apoptotic effect of these agents. These findings are the first indication that Bfl-1 plays a crucial role in setting the elevated threshold of resistance of this malignant cell type to apoptosis.
(Copyright © 2011 UICC.)
Databáze: MEDLINE
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