Open AccessIdentification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family.
Author(s) -
Maurizio Orlandini,
Lucia Marconcini,
Rebecca Ferruzzi,
Salvatore Oliviero
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.21.11675
Subject(s) - growth factor , platelet derived growth factor , biology , platelet derived growth factor receptor , northern blot , microbiology and biotechnology , gene expression , vascular endothelial growth factor c , transfection , immediate early gene , vascular endothelial growth factor , complementary dna , gene , vascular endothelial growth factor a , cancer research , genetics , vegf receptors , receptor
Using a mRNA differential screening of fibroblasts differing for the expression of c-fos we isolated a c-fos-induced growth factor (FIGF). The deduced protein sequence predicts that the cDNA codes for a new member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. Northern blot analysis shows that FIGF expression is strongly reduced in c-fos-deficient cells. Transfection of exogenous c-fos driven by a constitutive promoter restores the FIGF expression in these cells. In contrast, both PDGF and VEGF expression is unaffected by c-fos. FIGF is a secreted dimeric protein able to stimulate mitogenic activity in fibroblasts. FIGF overexpression induces morphological alterations in fibroblasts. The cells acquire a spindle-shaped morphology, become more refractive, disorganized, and detach from the plate. These results imply that FIGF is a downstream growth and morphogenic effector of c-fos. These results also suggest that the expression of FIGF in response to c-fos activation induces specific differentiation patterns and its aberrant activation contributes to the malignant phenotype of tumors.