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Differential roles of Fos and Jun proteins in regulation of differentiation and apoptosis of v-myb-transformed monoblasts

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ZAHRADNÍČKOVÁ Eva ŠEVČÍKOVÁ Sabina SOUČEK Karel KUBALA Lukáš ŠMARDA Jan

Rok publikování 2003
Druh Článek ve sborníku
Konference Antibody-based therapeutics for cancer
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Onkologie a hematologie
Klíčová slova Fos; Jun; apoptosis; differentiation; monoblast
Popis The line of v-myb-transformed chicken monoblasts BM2 constitutively express v-myb oncogene of AMV. v-Myb causes differentiation block, high proliferation rate and resistance to apoptosis similarly as in v-myb-transformed myeloid precursor primary cells. Differentiation capability of BM2 cells to macrophage-like cells can resume by phorbol esters that activate PKC and transcription from promoters containing TRE. The fact that transcription factor AP-1 binds TRE prompted us to investigate the role of individual components of AP-1 - the Jun and Fos proteins in regulation of differentiation, proliferation and apoptosis of BM2 cells. We ectopically expressed c-Jun, c-Fos, v-Jun and v-Fos proteins in BM2 cells and compared their effects. We found that c-Fos but not c-Jun protein was capable to induce apoptosis of BM2 cells. Interestingly, transforming variant of the Fos protein (v-Fos) lost capacity of its cellular precursor to cause apoptosis of BM2 cells. On contrary, c-Jun but not c-Fos protein induced differentiation of BM2 cells to adherent macrophage-like cells. Both Fos and Jun proteins down-regulated proliferation of BM2 cells suggesting that individual components of AP-1 transcription factor possess distinct roles in determination of cell afte. Therefore, the presence of both Jun and Fos proteins in the cell seems to be optimal for tumor-suppressive processes.
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