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v-Jun and v-Fos proteins induce dedifferentiation of v-myb-transformed monoblasts

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ŠEVČÍKOVÁ Sabina ZAHRADNÍČKOVÁ Eva SOUČEK Karel ŠMARDA Jan

Rok publikování 2001
Druh Článek ve sborníku
Konference The Seventeenth Annual Meeting on Oncogene
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
Obor Onkologie a hematologie
Klíčová slova Myb; Fos; Jun; differentiation
Popis The fos/jun proto-oncogenes encode for proteins which are components of the AP-1 transcription complex that includes several Fos related and Jun related proteins. The AP-1 was shown to play multiple roles in functional development of hematopoietic precursor cells into mature blood cells. Proto-oncogenes of the fos/jun family are considered to be positive regulators of myeloid differentiation. Enforced c-fos and c-jun expression in certain myeloid leukemia cell lines results in increased propensity to differentiate. The line of v-Myb-transformed chicken monoblasts (BM2) can be induced to differentiate phorbol esters. Differentiation-promoting effects of 12-O-tetradecanoyl phorbol 13-acetate (TPA) on BM2 cells is carried though activation of protein kinase C followed by changes of activities of differentiation and proliferation regulators, including AP-1. To gain further insights into the role of fos/jun in leukemogenicity, BM2vJUN and BM2vFOS cell lines, which inducibly express v-jun and v-fos, respectively, were established. We found that either v-fos- or v-jun-expressing BM2 cells exhibit signs of dedifferentiation. They decrease ability to reduce NBT and increase expression of differentiation-specific markers as Mo-1 and MEP-17. This suggests that oncogenic forms of Jun and Fos proteins can further enforce v-Myb transformation.
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