Molecular biology and analysis of related genes of apoptosis in human gastric carcinomas and precancerous lesions

1. 1)正常胃粘膜中凋亡细胞极为罕见，而化生腺深部有少量凋亡细胞。计算30例管状腺瘤细胞凋亡数或凋亡指数（AI）。严重异型性管状腺瘤的AI高于轻度异型性管状腺瘤。分析了15例同时发现腺瘤和癌的手术切除胃的人工智能。前者的AI为4.9+2.1，后者为3.9+1.1，差异有统计学意义（P<0.05）。另一方面，肿瘤的增殖指数（PI）较高。2)携带野生型p53的15例胃癌的AI值为3.8+1.4，携带突变型p53的15例胃癌的AI值为4.9+1.2，后者显著高于后者（P<0.05）。3) 17例伴有淋巴样基质的eb病毒相关胃癌中AI显著低于其他组织学类型的胃癌（P<0.05）。术前连续静脉注射5-FU (500mg/d) 7 d的10例患者的AI值为6.1+3.6，未注射5-FU的10例患者的AI值为3.2+1.8 （P<0.05）。1) 1mM-5FU可诱导携带野生型p53基因的MKN-74和MKN-45发生细胞凋亡，携带突变型p53基因的MKN28和kto - iii p53基因缺失均未发生细胞凋亡。Western blot分析显示，在6株人胃癌细胞系中，检测到P53和P21在MKN-74和MKN-45.2中表达增加。携带野生型p53基因的MKN-74和MKN-45表达量最高。抗FAS抗体100ng/ml诱导细胞凋亡，AI值与FAS抗原表达水平相关。3) 1 μ M紫杉醇对人胃癌细胞系的阻滞作用在G2/M，随后引起细胞凋亡。紫杉醇易感性与p53基因状态无关。综上所述，多种刺激可诱导胃癌细胞发生不同程度的凋亡，而与凋亡相关的信号转导部分依赖于p53蛋白。少

1. in vivo analysis1) Apoptotic cells were extremely rare in normal gastric mucosa, whle a few apoptotic cells were present in deeper portions of the metaplastic glands. The number of apoptotic cells or apoptotic index (AI) was counted in 30 tubular adenomas. AI was higher in the tubular adenomas with severe atypia than in those with mild atypia. AI was analyzed in 15 surgically removed stomachs in which adenoma and carcinoma were found simultaneously. AI was 4.9+2.1 in the former and 3.9+1.1 in the latter, the value being significantly different (P<0.05). On the other hand, proliferative index (PI) was higher in the carcinomas.2) AI was 3.8+1.4 in 15 gastric cancers carrying wild type p53 and 4.9+1.2 in 15 cancers carrying mutated p53 gene, the value being significantly higher in the latter (P<0.05).3) AI was significantly lower in 17 EB-virus related gastric carcinomas with lymphoid stroma than other any histological type of gastric carcinomas (P<0.05).4) AI increased significantly t … More o 6.1+3.6 in 10 patients received continuous intravenous 5-FU at 500mg/day for 7 days preoperatively, compared with 10 patients without 5-FU (3.2+1.8 : P<0.05).2. in vitro analysis1) 1mM-5FU variably induced apoptosis in MKN-74 and MKN-45, both of which carries wild type p53 gene, but not MKN28 carrying mutated p53 gene and KATO-III p53 gene being deleted. Western blot analysis showed increasing of P53 and P21 in MKN-74 and MKN-45.2) Fas was detected to be expressed variably in the six human gastric carcinoma cell lines. The expression level was highest for MKN-74 and MKN-45 carrying wild type p53 gene. Anti-Fas antibody of 100ng/ml induced apoptosis, the value of AI being correlated with the expression levels of FAS antigen.3) Treatment with taxol of 1 uM arrested in G2/M,followed by apoptosis in the human gastric carcinoma cell lines. Susceptibility to taxol did not correlate with p53 gene status.These results overall indicate that gastric cancer cells might be variably induced apoptosis by a variety of stimuli, and signal transduction relating apoptosis partly depends on the p53 protein. Less