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Publication : Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways.

First Author  Claffey KP Year  1992
Journal  J Biol Chem Volume  267
Issue  23 Pages  16317-22
PubMed ID  1644816 Mgi Jnum  J:28222
Mgi Id  MGI:75847 Doi  10.1016/s0021-9258(18)42003-0
Citation  Claffey KP, et al. (1992) Vascular endothelial growth factor. Regulation by cell differentiation and activated second messenger pathways. J Biol Chem 267(23):16317-22
abstractText  Vascular endothelial growth factor (VEGF) is an angiogenic polypeptide that has been isolated from a variety of tumorigenic and nontransformed cell lines. Because of the importance of blood vessel growth to cell and tissue development, we have examined VEGF gene expression in a variety of mouse tissues and rodent models of cellular differentiation. Using a cloned murine VEGF cDNA we show that VEGF mRNA is expressed at relatively low levels in many adult mouse tissues examined. However, this message is dramatically induced in two models of cell differentiation: 3T3-adipose conversion and C2C12 myogenic differentiation. VEGF protein secretion is also induced in adipocyte differentiation. VEGF mRNA is markedly regulated in a pheochromocytoma (PC12) cell model of transformation and differentiation. The transformed undifferentiated cells express moderate levels of VEGF mRNA and this expression is virtually extinguished when cells differentiate into non-malignant neuron-like cells. Experiments employing phorbol esters and cAMP analogues indicate that VEGF mRNA expression is stimulated in preadipocytes by both protein kinase C and protein kinase A-mediated pathways. These results suggest that VEGF mRNA levels are closely linked to the process of cellular differentiation; they also clearly demonstrate that expression of this angiogenic factor is specifically regulated in a transformed cell line, possibly via aberrant activation of cellular second messenger pathways.
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