OVER-EXPRESSION OF FGFR2 IIIC ISOFORM ENHANCES THE GROWTH OF PANCREATIC CANCER

Abstract

Background: Fibroblast growth factor receptors (FGFRs) possess IIIb and IIIc isoforms, due to the alternative splicing of the carboxy-half of third immunoglobulin (Ig)-like domain. IIIb isoforms of FGFRs are mainly localized in epithelial cells, whereas IIIc isoforms are expressed in mesenchymal cells. We previously reported that expression of FGFR2 IIIb isoform in pancreatic cancer correlates with venous invasion and VEGF-A expression. In the present study, we examined expression and the role of FGFR2 IIIc in pancreatic cancer. Methods: FGFR2 IIIc and IIIb mRNA expression levels were examined in six pancreatic cancer cell lines by real-time PCR. FGFR2 IIIc cDNA was subcloned into pIRES2-EGFP vector and FGFR2 IIIc stably transfected KLM-1 cells were prepared. Growth rates of the FGFR2 IIIc transfected KLM-1 cells were compared with mock cells. Immunohistochemical analysis using anti-FGFR2 IIIc antibody was performed on 47 pancreatic cancer cases. Results: FGFR2 IIIc and IIIb expression was detected in all pancreatic cancer cell lines. FGFR2 IIIc was low in KLM-1, Capan-1, PK-1 and PK-8, whereas IIIb was highly expressed in the cells. Growth rate of FGFR2 IIIc stably transfected KLM-1 cells was higher than those of mock cells. FGFR2 IIIc was not localized in exocrine and endocrine components of normal pancreas, but it was strongly localized in cancer cells of 32 of 47 cases (68%). Conclusion: FGFR2 IIIc was expressed in many of pancreatic cancer cases and its expression may correlate with the cancer cell growth.