| First Author | Cheng N | Year | 2004 |
| Journal | Oncogene | Volume | 23 |
| Issue | 21 | Pages | 3770-80 |
| PubMed ID | 15034548 | Mgi Jnum | J:89924 |
| Mgi Id | MGI:3041931 | Doi | 10.1038/sj.onc.1207478 |
| Citation | Cheng N, et al. (2004) Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival. Oncogene 23(21):3770-80 |
| abstractText | 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. |
