Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene

Abstract

Purpose:The basic fibroblast growth factor (FGF-2) gene is bidirectionally transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS has been implicated in the posttranscriptional regulation of FGF-2 expression. The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer and to correlate their expression with clinicopathologic findings and outcome. Experimental Design: Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48 esophageal cancers relative to matched histologically normal esophageal epithelia (internal control). We used Cox proportional hazards analysis to calculate hazard ratios for recurrence and survival of patients with underexpression relative to the overexpression of FGF-2 and/or FGF-AS. Results: Overexpression of FGF-2 mRNA, by comparison with tumors underexpressing FGF-2, was associated with significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95% confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11; 95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were considered simultaneously, the association of FGF-2 mRNA overexpression with recurrence and mortality was even more pronounced, whereas FGF-AS mRNA overexpression was associated with reduced risk for recurrence and improved survival. Conclusions: Overexpression of FGF-2 mRNA is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the effect of FGF-2 expression and may have potential clinical application to the development of novel therapeutic strategies.

Comparative study of mouse and human feeder cells for human embryonic stem cells

“…First, no FGF-2 protein could be detected in CF 1-derived fibroblasts or in CF 1 fibroblast-conditioned media, although CF 1 fibroblasts expressed FGF-2 mRNA. This could be explained by the presence of antisense FGF mRNAs, which have been implicated in the posttranscriptional regulation of FGF-2 expression (Barclay et al, 2005). These antisense mRNAs could be over-expressed in CF 1-derived fibroblasts (our unpublished data).…”

Change in fibroblast growth factor 2 expression as an early phase radiotherapy‐responsive marker in sequential biopsy samples from patients with cervical cancer during fractionated radiotherapy

“…14 It has been demonstrated that FGF2 has prognostic value in several malignancies, including esophageal cancer, renal cell carcinoma, ovarian cancer, lung cancer, and uterine endometrial cancer. [15][16][17][18][19][20] The down-regulation of FGF2 messenger RNA expression may be associated with increased severity of CC. 21 FGF2 can be released from both tumor cells and stromal cells.…”

Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Carcinoma Cell Proliferation

“…FGF18, a specific ligand for FGFR3IIIc, is also upregulated in colorectal cancer (Shimokawa et al 2003), suggesting that FGFR3IIIc imparts changes such as cell proliferation and migration by mediating the effects of FGF18 effects in colorectal cancer (Sonvilla et al 2010). In EC, a previous study demonstrated that the expression of FGF2, a specific ligand for FGFR3IIIc, is upregulated in the patients with poor prognosis (Barclay et al 2005). …”