Identification of a c-fos-induced gene that is related to the platelet-derived growth factor/vascular endothelial growth factor family.

Abstract

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.

Genomic Organization of Human and Mouse Genes for Vascular Endothelial Growth Factor C

“…Thus, besides the significant differences in its exon structure and encoded protein domains, the VEGF-C gene also has interesting differences in its regulation and function in comparison with the VEGF prototype of this gene family (13,32). Interestingly, if gaps introduced into the amino acid sequences for the purposes of alignment are ignored for calculations, the newly cloned FIGF/VEGF-D is about 48% identical with human VEGF-C and about 31% identical with human VEGF (48,52). On the basis of their multiple amino acid sequence alignments, VEGF-C and VEGF-D are likely to have similar structural and functional properties and gene structures.…”

Role of COX-2 in lymphangiogenesis and restoration of lymphatic flow in secondary lymphedema

“…36,37 Because COX-2 inhibition reduced VEGF-C expression in the early stages of the experiment (Figure 4a), but not VEGF-D (Figure 4b), VEGF-C may be the growth factor responsible for enhancement of lymphangiogenesis. The transcription factors and regulatory promoter elements that control VEGF-D gene expression have not been fully identified; 38 however, VEGF-D may cooperate with VEGF-C in a COX-2-dependent manner. We previously reported that EP3 signaling activates AP-1 in fibroblasts.…”

Regulation of Vascular Endothelial Growth Factor D by Orphan Receptors Hepatocyte Nuclear Factor-4α and Chicken Ovalbumin Upstream Promoter Transcription Factors 1 and 2

“…3D, lane 9, middle and bottom). Previous studies suggested that transcription factor AP-1 may regulate vegf-D gene transcription via an AP-1 consensus site located in the human vegf-D 5 ¶-flanking region (12). Our studies revealed that the loss of a putative AP-1 site at À192 had no influence on basal vegf-D promoter activity ( Fig.…”

“…In another report, it was shown that a h-catenindependent mechanism can down-regulate vegf-D expression by influencing mRNA stability (11). Because the human vegf-D cDNA was initially isolated using an activator protein (AP-1) overexpression strategy (12), it was suggested that AP-1 may be directly involved in regulation of vegf-D gene expression. Because the transcription factors and regulatory promoter elements controlling vegf-D gene expression have not yet been identified, the role of AP-1 in regulation of VEGF-D, however, remains hypothetical.…”