Bcl-2 expression in F-MuLV-induced erythroleukemias: a role for the anti-apoptotic action of Bcl-2 during tumor progression

Continuous Fli-1 expression plays an essential role in the proliferation and survival of F-MuLV-induced erythroleukemia and human erythroleukemia

“…6 To this respect, the expression of bcl-2 in CB3 cells infected with En/Fli-1 was much lower than cells infected with the control vector alone. These data suggest that the fli-1 proto-oncogene contributes to cell survival, at least in part, by the upregulation of bcl-2 in erythroleukemic cells, 24 resulting in evasion of the normal apoptotic program.…”

“…The anti-apoptotic gene, bcl-2, overexpressed in F-MuLVinduced erythroleukemias, 24 has previously been shown to be a direct Fli-1 target gene, and Fli-1-mediated Bcl-2 upregulation contributes to the enhanced survival of erythroblasts. 6 Consequently, the direct transcriptional regulation of Fli-1 target genes, such as bcl-2, is thought to contribute to the transforming ability of Fli-1 in erythroleukemic cells.…”

Paradoxical role of apoptosis in tumor progression

“…Moreover, in some experimental system, we can find examples of the mutual exclusion of these two anti-apoptotic factors: erythroleukemia cell lines, induced by F-MuLV frequently overexpress bcl-2 and this event was shown to precede the emergence of p53 mutations, suggesting that bcl-2 expression may delay p53 mutation in leukemic cells [Howard et al, 2001]. Interestingly, the majority of F-MuLVinduced erythroleukemia cell lines established from primary tumors induced in p53-deficient mice express low to negligible levels of bcl-2 [Howard et al, 2001].…”

Erythroblast Transformation by FLI-1 Depends upon Its Specific DNA Binding and Transcriptional Activation Properties

“…Our previous studies (27) have shown that BCL-2 is a direct target of FLI-1 in primary erythroblasts and that up-regulation of BCL-2 expression is involved in the ability of FLI-1 to induce erythroblast survival in the absence of hEpo. Two other genes were identified by differential screening to be strongly up-regulated in FLI-1-transformed erythroblasts: the first encodes SLAP, a SH2-and SH3-domain adaptor, and the second encodes inositol polyphosphate 5Ј-phosphatase ( (45) (27,46). The ability of FLI-1 to inhibit erythroblast differentiation has been proposed to involve FLI-1-mediated repression of retinoblastoma gene transcription (7).…”