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.

P75NTRp75NTR在所有食管鳞癌组织中均有表达，p75NTR阳性表达比例平均为30.1%。P75NTR阳性克隆的大小大于p75NTR阴性克隆(p&lt；0.0001)。SiRNA下调p75NTR的表达可明显抑制细胞生长并诱导细胞凋亡。我们的研究结果表明，在ESCC细胞系中有少量细胞表达p75NTR，p75NTR对于ESCC肿瘤的生存和维持是必需的。61%的患者可以检测到ABCG2ABCG2的表达，ABCG2阳性细胞的比例可变(0%到100%)。多因素分析显示，肿瘤中ABCG2阳性细胞的存在与原发肿瘤的范围和阳性的淋巴结转移有关。我们的结果提示ABCG2在食管癌的恶性特征中起重要作用。在表达Hedgehog(HH)途径分子的细胞系中，环多巴胺显著抑制细胞的增殖和迁移，而在Shh和Gli-1缺乏表达的细胞系中，细胞的增殖没有受到影响。针对Gli-1的siRNA可抑制食管鳞癌细胞的生长。FHITNicotine诱导FHIT基因甲基化，减弱FHIT蛋白，并与DNMT3a在正常食道上皮细胞(HEEC)的表达有关。此外，停止中长期尼古丁暴露后，HEECs中FHIT蛋白再次表达，NGFNGF过度表达与食道癌患者的淋巴结转移、远处转移、TNM分期高、肿瘤分化差、生存不良有关。TrkA抑制剂NGF抗体和NGF-小干扰RNA在Transwell迁移实验中均显著降低了高表达NGF的人鳞状细胞癌细胞系HSA/c的运动能力。

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.