Research projects

2. Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Cancer Malignant Progression.

More than 90% of esophagus cancer is squamous cell carcinoma. The esophageal squamous cell carcinoma (ESCC) is an invasive and progressive cancer. The percentage of patients in which there is lymph node metastasis of ESCC is more than 30% that is quite high compared with other digestive tract cancers, for example 11.9% in gastric cancer and 10 % in sigmoid colon cancer. The ESCC is well known to show poor prognosis, and 5-year overall survival remains approximately 20% despite the use of multimodal treatments such as extensive surgery.
The expression of FGFR isoforms is temporally and spatially regulated in embryos and in normal adult organs. Alternative splicing of the FGFR gene has been implicated in carcinogenesis. Switch expression of FGFR to mesenchymal isoforms, enabling cells to receive signals usually restricted to the connective tissue. FGFR3 has two different transmembrane-type isoforms, FGFR3 IIIb and IIIc, which are produced by alternative splicing and have distinctive ligand-specificities. In normal tissues, IIIb isoform is mainly expressed in the epithelium, whereas IIIc isoform is mainly expressed in the mesenchyme.  Previously, we have found the expression of FGFR3 IIIc isoforms in 86 % of the ESCC specimens tested by RT-PCR was enhanced. Thus, it suggests that enhanced expression of FGFR3 IIIc isoform may promote the malignant progression of ESCC. The aim of our study is to elucidate the mechanism of promoting malignant progression by enhanced expression of FGFR3 IIIc isoform.