Detection of dormancy-regulating factors and the related proteins in the proliferation and progression of human gastrointestinal carcinomas

1.活体分析：(1)胃腺瘤处于休眠状态。与粘膜内型胃癌相比，腺瘤的细胞凋亡指数(AI)明显升高，增殖活性明显降低，这可能与肿瘤内微血管密度及胸苷磷酸化、环氧合酶(COX)-2、和P53的表达有关。(2)RUNX3基因可能是一种抑癌基因，在胃主细胞和G细胞以及食道粘膜表层细胞和肺泡细胞中表达，而在食管癌、胃癌、口腔癌和支气管癌中的表达明显降低。(3)新证实的ARPP基因在包括心肌在内的肌肉组织中表达，失神经支配后表达减弱。(4)口腔癌、食道癌、胃癌、支气管癌和MFH均有COX-2的免疫组织化学表达，其表达与IMVD、AI和Skp2的表达有关。(5)FHIT的表达与MLH1相关，而与P53的表达及胃癌、结肠癌和胆囊癌的早期致癌事件无关。(2)COX-2选择性抑制剂抑制人食道癌和胃癌细胞的增殖和细胞周期，但不诱导细胞凋亡。(3)Fas诱导的细胞凋亡的信号转导是通过线粒体途径进行的，其信号转导受PI3K-Akt激活的影响。PI3K-Akt抑制剂促进肿瘤细胞凋亡。3.获得了针对ARPP、RUNX3和RUNX3表达载体的特异性抗体。成功培育出ARPP基因敲除小鼠。

1.in vivo analysis(1)Gastric adenomas are considered to be in dormancy. Comparing with the intramucosal gastric carcinomas, the adenomas showed significantly higher apoptotic index (AI) and lower proliferative activity, which might correlated with intratumoral microvessel density(IMVD) and the expression of thymidine phosphorylase、cyclo-oxygenase(COX)-2、and P53.(2)RUNX3, a possible tumor suppressor gene, was demonstrated to express in gastric chief cells and G ells, as well as superficial cells of esophageal mucosa and lung alveolar cells, in contrast to obvious lower expression in esophageal, gastric, oral and bronchial carcinomas, in the both operative specimens and cultured cell lines.(3)A newly confirmed ARPP gene showed to express in the muscle including cardiac muscle and the expression was decreased by denervation.(4)Human oral, esophageal, gastric, bronchial carcinomas and MFH showed immunohistochemical expression of COX-2, which correlated with IMVD and AI, as well as Skp2 expression.(5)Fhit expression was correlated with Mlh1, but not P53 expression and early events of carcinogenesis in the gastric, colonic and gall bladder carcinomas.2.in vitro analysis(1)RUNX3 gene transfection resulted in cell cycle arrest, but not apoptosis in the human gastric carcinoma cell lines.(2)COX-2 selective inhibitor caused suppression of cell proliferation and cell cycle arrest, but not apoptosis in the esophageal and gastric carcinoma cell lines.(3)Signal transduction of Fas-induced apoptosis was conducted via mitochondrial pathway, which was affected by PI3K-Akt activation. PI3K-Akt inhibitor enhanced tumor cell apoptosis.3.Others(1)Specific antibodies for ARPP and RUNX3 and RUNX3 expression vector were generated. ARPP knock-out mouse was successfully produced.