Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family.
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.
Orlandini
M
M
Dipartimento di Biologia Molecolare Università di Siena, Italy.
Marconcini
L
L
Ferruzzi
R
R
Oliviero
S
S
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D016228:Endothelial Growth Factors / Q000737:chemistry; D005347:Fibroblasts; D005786:Gene Expression Regulation; D016762:Genes, fos; D006133:Growth Substances / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D008222:Lymphokines / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D006133:Growth Substances; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D042442:Vascular Endothelial Growth Factors; D013936:Thymidine