当前位置： SCI文献检索 > ONCOGENE期刊下所有文献 > FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts.

FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts.

Abstract：

:Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed in about 75% of the erythroleukemias induced by the F-MuLV helper virus in newborn mice. To analyse the consequences of the enforced expression of FLI-1 on erythroblast differentiation and proliferation and to compare its activity to that of PU.1/Spi-1, we used a heterologous system of avian primary erythroblasts previously described to study the cooperation between Spi-1/PU.1 and the other molecular alterations observed in SFFV-induced disease. FLI-1 was found: (i) to inhibit the apoptotic cell death program normally activated in erythroblasts following Epo deprivation; (ii) to inhibit the terminal differentiation program induced in these cells in response to Epo and; (iii) to induce their proliferation. However, in contrast to Spi-1/PU.1, the effects of FLI-1 on erythroblast, differentiation and proliferation did not require its cooperation with an abnormally activated form of the EpoR. Enhanced survival of FLI-1 expressing erythroblasts correlated with the upregulation of bcl2 expression. FLI-1 also prevented the rapid downregulation of cyclin D2 and D3 expression normally observed during Epo-induced differentiation and delayed the downregulation of several other genes involved in cell cycle or cell proliferation control. Our results show that overexpression of FLI-1 profoundly deregulates the normal balance between differentiation and proliferation in primary erythroblasts. Thus, the activation of FLI-1 expression observed at the onset of F-MuLV-induced erythroleukemia may provide a proliferative advantage to virus infected cells that would otherwise undergo terminal differentiation or cell death.

journal_name

Oncogene

journal_title

Oncogene

authors

Pereira R,Quang CT,Lesault I,Dolznig H,Beug H,Ghysdael J

doi

10.1038/sj.onc.1202534

subject

Has Abstract

pub_date

1999-02-25 00:00:00

pages

1597-608

issue

eissn

0950-9232

issn

1476-5594

journal_volume

pub_type

杂志文章

在线工具

FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts.