Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis.

Eischen CM, Woo D, Roussel MF, Cleveland JL
Mol Cell Biol. 2001 21 (15): 5063-70

PMID: 11438662 · PMCID: PMC87232 · DOI:10.1128/MCB.21.15.5063-5070.2001

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 Emu-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 Emicro-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.

MeSH Terms (20)

ADP-Ribosylation Factor 1 Animals Apoptosis bcl-X Protein Blotting, Northern Blotting, Western Cells, Cultured Cell Survival Lymph Nodes Mice Mice, Knockout Mice, Transgenic Myeloid Cells Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-myc RNA Stem Cells Time Factors Transformation, Genetic Tumor Suppressor Protein p53

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