TEL, a putative tumor suppressor, induces apoptosis and represses transcription of Bcl-XL

The ETS family transcriptional repressor TEL is frequently disrupted by chromosomal translocations, including the t(12;21) in which the second allele of TEL is deleted in up to 90% of the cases. Consistent with its role as a putative tumor suppressor, TEL expression inhibits colony formation by Ras-transformed NIH 3T3 cells and hinders proliferation of a variety of cell types. Although we observed no alteration in the cell cycle of TEL-expressing cells, we did find a marked increase in apoptosis of serum-starved TEL-expressing NIH 3T3 cells. This decrease in cell survival required the DNA binding domain of TEL, suggesting that TEL repressed an antiapoptotic gene. These observations prompted us to search for genes regulated by ETS family proteins that regulate apoptosis. The anti-apoptotic molecule Bcl-X-L contains multiple ets-factor binding sites within its promoters, and TEL repressed a Bcl-X-L promoter-linked reporter gene. Moreover, the enforced expression of TEL decreased the endogenous expression of both Bcl-X-L mRNA and protein. TEL-mediated repression of Bcl-X-L likely affects cell survival via regulation of the apoptotic pathway.