Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival

Ningli Cheng; Yelena M Janumyan; Lisa Didion; Chris Van Hofwegen; Elizabeth Yang; C Michael Knudson

doi:10.1038/sj.onc.1207478

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Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival

Journal article

Peer reviewed

Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival

Ningli Cheng, Yelena M Janumyan, Lisa Didion, Chris Van Hofwegen, Elizabeth Yang and C Michael Knudson

Oncogene, Vol.23(21), pp.3770-3780

05/06/2004

DOI: 10.1038/sj.onc.1207478

PMID: 15034548

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Abstract

Bcl-2 promotes oncogenesis by inhibiting cell death. Bcl-2 also inhibits proliferation and suppresses tumorigenesis in some settings. To clarify the role of the antiproliferative function of Bcl-2, mice expressing a mutant form of Bcl-2 reported to lack antiproliferative activity were generated (tyrosine 28 to alanine, Bcl-2-Y28A). As expected, both wild type (WT) and Bcl-2-Y28A inhibited apoptosis similarly. In contrast to previous results in cell lines, Bcl-2-Y28A inhibited T-cell proliferation identical to WT-Bcl-2. Significantly, both Bcl-2-Y28A and WT-Bcl-2 inhibited proliferation of T cells isolated from older animals, but not proliferation of T cells from immature mice. Instead, inhibition of cell activation correlated with T-cell size, p27 levels, and RNA content, all indicators of quiescent G0 arrest. Consistent with this model, Bcl-2 inhibition of T-cell proliferation was reversed by expression of Bax, again correlating cell proliferation with cell size. These experiments do not support genetically separate effects of Bcl-2 on apoptosis and proliferation. Instead, the data support a model in which Bcl-2 and Bax regulate T-cell proliferation by changes in T-cell size and by increasing the markers of quiescent G0 arrest. These changes likely result from prolonged T-cell survival.

Pyronine - analysis

T-Lymphocytes - physiology

Proto-Oncogene Proteins c-bcl-2 - physiology

Age Factors

Cell Survival

Lymphocyte Activation

Microfilament Proteins - analysis

Mice, Transgenic

bcl-2-Associated X Protein

Muscle Proteins

Animals

Cell Cycle

Proto-Oncogene Proteins - physiology

T-Lymphocytes - immunology

Mice

Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - physiology

Apoptosis

Details

Title: Subtitle: Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival
Creators: Ningli Cheng - Department of Pathology, The University of Iowa Roy J and Lucille P Carver College of Medicine, 3160 ML, Iowa City, IA 52242, USA
Yelena M Janumyan
Lisa Didion
Chris Van Hofwegen
Elizabeth Yang
C Michael Knudson
Resource Type: Journal article
Publication Details: Oncogene, Vol.23(21), pp.3770-3780
DOI: 10.1038/sj.onc.1207478
PMID: 15034548
NLM abbreviation: Oncogene
ISSN: 0950-9232
eISSN: 1476-5594
Publisher: England
Grant note: T32GM08554 / NIGMS NIH HHS 1R01CA88967 / NCI NIH HHS 1R01CA78443 / NCI NIH HHS
Language: English
Date published: 05/06/2004
Academic Unit: Pathology; Radiation Oncology; Teaching and Learning
Record Identifier: 9984046920702771

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