| First Author | Eischen CM | Year | 2001 |
| Journal | Mol Cell Biol | Volume | 21 |
| Issue | 15 | Pages | 5063-70 |
| PubMed ID | 11438662 | Mgi Jnum | J:70387 |
| Mgi Id | MGI:2137142 | Doi | 10.1128/MCB.21.15.5063-5070.2001 |
| Citation | Eischen CM, et al. (2001) Apoptosis Triggered by Myc-Induced Suppression of Bcl-X(L) or Bcl-2 Is Bypassed during Lymphomagenesis. Mol Cell Biol 21(15):5063-70 |
| abstractText | Enforced Bcl-2 expression inhibits Myc-induced apoptosis and cooperates with Myc in transformation. Here we report that the synergy between Bcl-2 and Myc in transforming hematopoietic cells in fact reflects a Myc-induced pathway that selectively suppresses the expression of the Bcl-X(L) or Bcl-2 antiapoptotic protein. Myc activation suppresses Bcl-X(L) RNA and protein levels in cultures of primary myeloid and lymphoid progenitors, and Bcl-X(L) and Bcl-2 expression is inhibited by Myc in precancerous B cells from E&mgr;-myc transgenic mice. The suppression of bcl-X RNA levels by Myc requires de novo protein synthesis, indicating that repression is indirect. Importantly, the suppression of Bcl-2 or Bcl-X(L) by Myc is corrupted during Myc-induced tumorigenesis, as Bcl-2 and/or Bcl-X(L) levels are markedly elevated in over one-half of all lymphomas arising in E&mgr;-myc transgenic mice. Bcl-2 and/or Bcl-X(L) overexpression did not correlate with loss of ARF or p53 function in tumor cells, indicating that these two apoptotic pathways are inactivated independently. Therefore, the suppression of Bcl-X(L) or Bcl-2 expression represents a physiological Myc-induced apoptotic pathway that is frequently bypassed during lymphomagenesis. |
