A novel isoform of human fibroblast growth factor 8 is induced by androgens and associated with progression of esophageal carcinoma

Human esophageal carcinomas occur more frequently in males, suggesting that androgens may play a role in the regulation of gene expression associated with malignant transformation. We previously established an androgen-sensit ive squamous cell carcinoma line, KSE-1, from a male patient with esophagea l cancer; recently a novel isoform of human fibroblast growth factor 8 (FGF 8f, isoform FGF8b) was identified and expressed following androgen stimulat ion of KSE-1 cells. The predicted amino acid sequence of FGF8f contained an additional 29 amino acids when compared to FGF8b, Flutamide, an androgen a ntagonist, inhibited both FGF8b and FGF8f transcription in a dose-dependent manner. Tissue analysis from tumors revealed FGF8b expression in 24 of 41 male, but in 0 of 9 female esophageal carcinomas (58.5%), and none in adjac ent normal esophageal mucosa. In addition, FGF8f was detected in 9 of 24 FG F8b-positive tumors (37.5%), and this observation was significantly associa ted with a poor prognosis (P < 0.001). Our observations suggest that androg enic exposure will induce FGF isoforms in tumor cells, and expression of th ese growth factors is associated with the prevalence and prognosis of esoph ageal carcinoma in males.