GROWTH, DIFFERENTIATION, AND TRANSFORMATION OF HUMAN ESOPHAGEAL CELLS

我们正在开发一种人类食道癌发生的体外模型。 将该策略用于其他类型的人类上皮细胞已被证明是成功的 细胞，一种正常人食道上皮细胞的无血清培养液 已经被开发出来了。沙门氏菌的病理生物学效应 12-0-十四酰佛波醇-13-乙酸酯，T-2毒素，香烟烟雾冷凝物 和乙醇进行了检测。用于与正常人的比较研究 食道上皮细胞，七种人食道癌细胞系 是在大型强子对撞机上新建立的。癌细胞株的数量较少 表皮生长因子受体的数量高于正常食管壁 上皮细胞。癌细胞呈异倍体，频率较高。 1、3、9和11号染色体的结构异常。 在3个癌细胞系中发现了11ql2的染色区域。 因为“永生化”似乎是人类细胞中一个限速步骤 体外致癌，正常食道上皮细胞 以pRSV-SV40为载体的磷酸锶共沉淀法转基因 T和一种细胞系(HET-IA)已经被开发出来，它已经经历了超过 人口翻番160人。HET-IA具有上皮形态，染色为 细胞角蛋白和SV40T抗原通过免疫荧光检测，并已保留 无瘤裸鼠的非致瘤性。 我们计划一种多方面的方法来从肿瘤上转变正常或SV40 “永生化”(HET-1a)人食道上皮细胞。细胞将会 接触化学致癌物(例如，N-甲基-N‘-亚硝脲或 苯并[a]芘二醇环氧化物)，用于改变生长性质 包括对末端鳞状分化诱导剂的抗性和 检查裸鼠的致瘤性。

We are developing an in vitro model of human esophageal carcinogenesis. Using the strategy proven successful for other types of human epithelial cells, a serum-free medium for normal human esophageal epithelial cells has been developed. The pathobiological effects of 12-0-tetradecanoylphorbol-13-acetate, T-2 toxin, cigarette smoke condensate and ethanol have been examined. For comparison studies with normal human esophageal epithelial cells, seven human esophageal carcinoma cell lines have been newly established in LHC. The carcinoma cell lines had fewer numbers of epidermal growth factor receptors than the normal esophageal epithelial cells. The carcinoma cells were aneuploid with frequent structural abnormalities in chromosomes 1, 3, 9 and 11. A homogeneously staining region at llql2 was found in 3 of the carcinoma cell lines. Since "immortalization" appears to be a rate-limiting step in human cell carcinogenesis in vitro, normal esophageal epithelial cells were transfected by strontium phosphate coprecipitation with a plasmid pRSV-SV40 T and a cell line (HET-IA) has been developed that has undergone more than 160 population doublings. HET-IA has an epithelial morphology, stains for cytokeratins and SV40 T antigen by immunofluorescence, and has remained nontumorigenic in athymic nude mice. We plan a multifaceted approach to neoplastically transform normal or SV40 T "immortalized" (HET-lA) human esophageal epithelial cells. The cells will be exposed to chemical carcinogens (e.g., N-methyl-N'-nitrosourea or benzo[a]pyrene diol epoxide), selected for altered growth properties including resistance to inducers of terminal squamous differentiation and examined for tumorigenicity in athymic nude mice.