Vav promotes differentiation of human tumoral myeloid precursors
| Autor: | Cinzia Carini, Carlo Mischiati, Silvano Capitani, Valeria Bertagnolo, Alessia Sereni, Alberto Bavelloni, Federica Brugnoli |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Myeloid
Cellular differentiation Gene Expression Cell Cycle Proteins HL-60 Cells Tretinoin Biology Transfection chemistry.chemical_compound Myeloproliferative Disorders Leukemia Promyelocytic Acute Cell Line Tumor Proto-Oncogene Proteins Stilbenes Tumor Cells Cultured medicine Humans Enzyme Inhibitors Phosphorylation RNA Small Interfering Proto-Oncogene Proteins c-vav Myeloid Progenitor Cells Regulation of gene expression Acute promyelocytic leukemia (APL) All-trans retinoic acid (ATRA) Granulocytic differentiation Tyrosine phosphorylation Vav Gene Expression Regulation Leukemic Cell Differentiation Cell Biology Protein-Tyrosine Kinases Haematopoiesis medicine.anatomical_structure chemistry Cancer research Granulocytes |
| Zdroj: | Experimental Cell Research. 306:56-63 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2004.12.001 |
| Popis: | Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders. |
| Databáze: | OpenAIRE |
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