Digestive Diseases and Sciences

, Volume 46, Issue 5, pp 1016–1021

A Novel Isoform of Human Fibroblast Growth Factor 8 Is Induced by Androgens and Associated with Progression of Esophageal Carcinoma


  • Shinji Tanaka
    • Department of Surgery II, Faculty of MedicineKyushu University
  • Hiroaki Ueo
    • Department of SurgeryOita Prefectural Hospital
  • Ken-ichi Mafune
    • Department of Surgery, Faculty of MedicineUniversity of Tokyo
  • Masaki Mori
    • Department of Surgery, Medical Institute of BioregulationKyushu University
  • Jack R. Wands
    • Liver Research Center, Rhode Island HospitalBrown University School of Medicine
  • Keizo Sugimachi
    • Department of Surgery II, Faculty of MedicineKyushu University

DOI: 10.1023/A:1010753826788

Cite this article as:
Tanaka, S., Ueo, H., Mafune, K. et al. Dig Dis Sci (2001) 46: 1016. doi:10.1023/A:1010753826788


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-sensitive squamous cell carcinoma line, KSE-1, from a male patient with esophageal cancer; recently a novel isoform of human fibroblast growth factor 8 (FGF8f, isoform FGF8b) was identified and expressed following androgen stimulation of KSE-1 cells. The predicted amino acid sequence of FGF8f contained an additional 29 amino acids when compared to FGF8b. Flutamide, an androgen antagonist, 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 adjacent normal esophageal mucosa. In addition, FGF8f was detected in 9 of 24 FGF8b-positive tumors (37.5%), and this observation was significantly associated with a poor prognosis (P < 0.001). Our observations suggest that androgenic exposure will induce FGF isoforms in tumor cells, and expression of these growth factors is associated with the prevalence and prognosis of esophageal carcinoma in males.

androgenFGF8, isoformesophageal carcinomasignal transduction

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© Plenum Publishing Corporation 2001