Research for esophageal carcinogenesis and proliferation, by characterization of cancer stem cells and analysis of the inactivation mechanism for suppressor genes in normal esophageal epithelial cells.

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p75NTRp75NTR was expressed in all examined esophageal squamous cell carcinoma (ESCC) and the mean proportion of the p75NTR-positive fraction was 30.1%. The size of p75NTR-positive colonies was larger than that of p75NTR-negative colonies (p<0.0001). Down regulation of p75NTR expression by SiRNA resulted in marked growth inhibition with induction of apoptosis. Our findings suggest that p75NTR was expressed in a small number of cells in ESCC cell lines and p75NTR is necessary for survival and maintenance of ESCC tumors.ABCG2ABCG2 expression was detectable in 61% of patients and the proportion of ABCG2 positive cells was variable (0% to 100%). The presence of ABCG2 positive cells in the tumor was revealed to be an independent prognostic factor along with the extent of the primary tumor and positive lymph node metastasis in multivariate analysis. Our data suggests that ABCG2 plays an underlying role in malignant characteristics of ESCC.GlilCell proliferation and migration were significantly inhibited by Cyclopamine in the cell lines that expressed all Hedgehog (Hh) pathway molecules, while cell proliferation was not affected in the cell lines lacking Shh and Gli-1 expression. SiRNA target for Gli-1 inhibited the cell growth of ESCC cells.FHITNicotine induced methylation of the FHIT gene and attenuated Fhit protein, associated with DNMT3a expression in normal esophageal epithelial cells (HEEC). Furthermore, re-expression of Fhit protein of HEECs was found after cessation of moderate- to long-term exposure to nicotine.NGFNGF overexpression was associated with lymph node metastasis, distant metastasis, higher TNM stage, poorer tumour differentiation and poorer survival of esophageal cancer patients. The motility of HSA/c, one of the ESCC cell lines overexpressing NGF, was significantly decreased by either neutralizing NGF antibody, an inhibitor of TrkA, or NGF-small interfering RNA in transwell migration assay.