Biological Roles of Fibroblast Growth Factor-2*

Bikfalvi, Andréas; Klein, Sharon; Pintucci, Giuseppe; Rifkin, Daniel B.

doi:10.1210/edrv.18.1.0292

Cited by 454 publications

(428 citation statements)

References 303 publications

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“…This cell line allowed us to show for the first time that novH expression is up-regulated by FGF2 and downregulated by TGF␤1, whereas IGF-I and II have no influence. These data suggested that FGF2 and TGF␤1, which are involved in the development of various tumors (69,70) and are also produced by adrenocortical cells (71,72), could be considered as potential candidates involved in the modulation of novH expression in adrenocortical tumors (19). Our results also show that TGF␤1 reduces the up-regulation of novH expression induced by FGF2, suggesting that the basal level of novH expression results from a balance between the actions of these two growth factors.…”

Section: Discussionsupporting

confidence: 67%

The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFβ1 through c-Jun in a Smad-independent Manner

Lafont

Laurent

Thibout

et al. 2002

Journal of Biological Chemistry

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The human NOV secreted glycoprotein (NOVH) is abundant in the fetal and adult adrenal cortex. The amount of NOVH increases in benign adrenocortical tumors and decreases in malignant adrenocortical tumors, suggesting that NOVH plays a role in tumorigenesis in the adrenal cortex. Transforming growth factor ␤1 (TGF␤1), fibroblast growth factor 2 (FGF2), and insulin growth factors (IGFs) play crucial roles in the physiology of the adrenal cortex. We investigated the effects of these factors on the expression of novH in the NCI H295R adrenocortical cell line. The amounts of NOVH protein and novH transcripts were down-regulated by TGF␤1 and up-regulated by FGF2, whereas IGFs had no effect. Furthermore, the TGF␤1-dependent inhibition of novH promoter activity was completely abrogated following site-directed mutation of two activating protein (AP-1) sequences (positions ؊473 and ؊447), whereas the stimulatory effect of FGF2 was not affected. Co-transfection with dominant negative forms of c-Jun and MEKK1 also abrogated novH-targeted regulation by TGF␤1, whereas the overproduction of Smad proteins or dominant negative forms of Smad had no effect. Taken together, these results suggest that c-Jun and MEKK1 signaling but not Smad signaling are involved in the TGF␤1-dependent decrease in NOVH in NCI H295R cells. In conclusion, our data provide evidence that novH is a new target of TGF␤1; unlike other members of the CCN (cyr61, ctgf, nov) family, however, its expression is repressed rather than induced.

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Section: Discussionsupporting

confidence: 67%

The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFβ1 through c-Jun in a Smad-independent Manner

Lafont

Laurent

Thibout

et al. 2002

Journal of Biological Chemistry

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“…This growth factor plays a key role in diverse biological processes, which are of particular interest to cancer biology, including proliferation, di erentiation, migration, survival and neovascularization (Bikfalvi et al, 1997). FGFs elicit their biological activities by binding to high a nity FGF receptor (FGFR) tyrosine kinases in the presence of heparin or heparan sulfate.…”

Section: Introductionmentioning

confidence: 99%

Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells

et al. 2001

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“…The role of FGF-2 in tumorigenesis has been largely documented (Bikfalvi et al, 1997). FGF-2 promotes cancerous cell survival and proliferation, and tumour neovascularization.…”

Section: Discussionmentioning

confidence: 99%

“…FGF-2 has been shown to stimulate endothelial cell growth and migration in vitro as well as in vivo angiogenesis and has long been considered as the principal tumour angiogenic factor (Kandel et al, 1991). FGF-2 is also implicated in wound-healing processes and has a potential oncogenic e ect (for review, see Bikfalvi et al, 1997). The multiple roles carried out by FGF-2 require a strong and subtle control of its synthesis.…”

Section: Introductionmentioning

confidence: 99%

“…The multiple roles carried out by FGF-2 require a strong and subtle control of its synthesis. Although numerous studies have described transcriptional regulations of FGF-2 expression, such regulations cannot account for the di erential expression of FGF-2 which is synthesized as ®ve molecular forms with di erent localization and functions (Arnaud et al, 1999;Bikfalvi et al, 1997;Florkiewicz and Sommer, 1989;Prats et al, 1989). Expression of the FGF-2 isoforms is translationally regulated by stress and cell density in normal human cells, whereas these isoforms are constitutively expressed in transformed cells (Galy et al, 1999;Vagner et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

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Tumour suppressor p53 inhibits human fibroblast growth factor 2 expression by a post-transcriptional mechanism

et al. 2001

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Fibroblast growth factor-2 (FGF-2) is a powerful mitogen and angiogenic factor whose expression is strongly regulated at the translational level. The constitutive upregulation of FGF-2 isoforms in transformed cells prompted us to investigate the posttranscriptional e ects of a tumour suppressor, p53, on FGF-2 expression. We show here in human primary skin ®broblasts that the cell density-dependent variation of FGF-2 mRNA translatability was inversely correlated with endogenous p53 expression. Transient cell transfection revealed an inhibitory e ect of wild-type p53 on the expression of chimeric FGF ± CAT proteins. RNAse mapping experiments ruled out any e ect of p53 on FGF ± CAT mRNA accumulation, suggesting a translational inhibition. This inhibition was mediated by the FGF-2 mRNA leader, but not by vascular endothelial growth factor or platelet derived growth factor mRNA leaders. Neither p53-like protein p73, nor p21/waf had any inhibitory activity. Furthermore a set of hot spot mutants of p53 bearing mutations in the DNA binding domain had no post-transcriptional inhibitory e ect. In contrast a p53 mutant of the transactivating domain was still able to block FGF ± CAT expression, indicating that the post-transcriptional activity of p53 described here was independent of the trans-activation of target genes. Such data reveal a novel mechanism by which p53 e ciently blocks the expression of a major proliferating, anti-apoptotic and angiogenic gene. Oncogene (2001) 20, 1669 ± 1677.

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Biological Roles of Fibroblast Growth Factor-2*

Cited by 454 publications

References 303 publications

The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFβ1 through c-Jun in a Smad-independent Manner

The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFβ1 through c-Jun in a Smad-independent Manner

Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells

Tumour suppressor p53 inhibits human fibroblast growth factor 2 expression by a post-transcriptional mechanism

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