Molecular-pathological study on the apoptosis-regulating factors and signal transduction in human gastrointestinal carcinomas

1)肿瘤细胞的凋亡指数与肿瘤内微血管密度(IMVD)呈显著正相关。2)腺病毒介导的野生型P53基因转移可导致细胞凋亡(MKN-1)、细胞停滞(MKN-45、74和Kato-III)和无效(TMK-1和OCUM-2M)，与P53基因状态无关。Bax的表达上调可能与MKN-1细胞的凋亡有关。3)Fas和Fas配体在人食管癌和胃癌前病变及癌组织中均有不同程度的表达，细胞凋亡通过Fas依赖和非依赖途径发生。Fas配体表达上调与胃肠道肿瘤的发生发展相关。人胃肠道癌组织中未发现Fas基因异常。4)胃肠癌不同程度地表达胸苷磷酸化酶和/或环氧合酶-2(COX-2)，两者均显著增加IMVD，减少肿瘤细胞的凋亡。5)一个新的Anirin重复蛋白ARPP，由333A.A.组成。是从人食道癌细胞系TE-1中克隆的。ARPP在正常骨骼肌、心肌以及各种胃肠道癌细胞系中均有表达。6)DNA复制调节因子微小染色体维持-2(MCM2)是一种新的、可靠的快速检测正常和肿瘤组织中增殖细胞的标志物。

1) Apoptotic index of the tumor cells and intratumoral microvessel density (IMVD) showed a significant correlation in human esophageal, gastric and colonic carcinomas.2) Adenovirus-mediated transfer of wild-type p53 gene resulted in apoptosis (MKN-1), cell arrest (MKN-45, 74 and KATO-III), and non-effectiveness (TMK-1 and OCUM-2M), regardless of p53 gene status. Upregulation of BAX might correlate with apoptosis of MKN-1 cells.3) FAS and FAS-ligand variably expressed in human esophageal and gastric precancerous lesions and carcinomas, in which apoptosis occurs via FAS-dependent and -independent pathway. Upregulation of FAS-ligand correlated with the progression of the human gastrointestinal carcinomas. No aberration of FAS gene was confirmed in human gastrointestinal carcinomas. Signal transduction through FAS occurs via mitochondria pathway.4) Gastrointestinal carcinomas variably expressed thymidine phosphorylase and/or cyclooxygenase-2(COX-2), both of which significantly caused increase of IMVD and decrease of apoptosis of the tumor cells.5) A novel ankirin repeated protein ARPP, consisted 333 a.a. was cloned from the human esophageal carcinoma cell line, TE-1. ARPP expressed in normal skeletal and cardiac muscle, as well as various gastrointestinal carcinoma cell lines. ARPP might play a significant role to inhibit apoptosis.6) DNA-replication regulating factor, minichromosome maintenance-2(MCM2) is a new, reliable marker for the rapid detection of proliferating cells in normal and neoplastic tissues.