GROWTH CONTROL IN EPITHELIAL CELLS AND ITS ALTERATION IN CARCINOGENESIS

肺泡II型肺上皮细胞是肺上皮细胞的起源细胞。 纤维化相关的周围型肺癌（瘢痕癌）， 人类癌症 这种类型的癌症的独特模型是由 结晶二氧化硅诱发的大鼠肺癌。 研究机制 在肺泡II型细胞的肿瘤转化，我们选择了 最近开发的胎鼠肺上皮细胞系FRLE（Leheup， BP等人，Lab Invest 60：791-807，1989）。 在目前的研究中，FRLE细胞 线的特点，并发现保留板层体和其他 原始细胞的超微结构特征。 FRLE线，传代时 38，被发现是非整倍体，与大多数染色体计数在 亚四倍体范围和2条标记染色体，但不致瘤 在裸鼠中。 发现该细胞系的细胞内化二氧化硅 细胞质中的颗粒;少量颗粒，大多较小 小于0.4 μ m的分布于细胞核内。 为了获得 在这种细胞类型的肿瘤表型中，FRLE细胞被转化为 用质粒pZipyK 12 yCys进行脂质体转染，该质粒携带K-ras癌基因， 密码子12上Gly至Cys突变。 大多数细胞系显示， 肿瘤形态，并在裸鼠中高度致瘤性， 在未分化癌中。 少数转染细胞系具有接近正常的 形态学不具有致瘤性。通过电子显微镜，ras- 转化的细胞系显示核异常和板层细胞丢失， 尸体 将ras-转化的线用作参考标准， 制定标准的过程中，选择转化 菌落和转化试验，适用于 二氧化硅和其他致癌物质的转化。

Alveolar type II pulmonary epithelial cells are the cells of origin of fibrosis-associated peripheral lung cancer (scar cancer), a major form of human cancer. A unique model for this type of cancer is provided by crystalline silica-induced lung carcinomas in rats. To study mechanisms of neoplastic transformation in alveolar type II cells, we chose the recently developed cell line of fetal rat lung epithelium, FRLE (Leheup, BP et al, Lab Invest 60:791-807, 1989). In present studies, the FRLE cell line was characterized and found to retain lamellar bodies and other ultrastructural features of the cell of origin. The FRLE line, at passage 38, was found to be aneuploid, with most chromosome counts in the hypotetraploid range, and 2 marker chromosomes, but it was not tumorigenic in nude mice. The cells of this line were found to internalize silica particles in their cytoplasm; a small number of particles, mostly smaller than 0.4 microm, were localized within nuclei. In order to obtain a neoplastic phenotype of this cell type, FRLE cells were transformed by lipofection with plasmid pZipyK12yCys, carrying a K-ras oncogene with a Gly to Cys mutation on codon 12. Most of the resulting cell lines showed neoplastic morphology and were highly tumorigenic in nude mice, resulting in anaplastic carcinomas. A few transfected cell lines with near-normal morphology were not tumorigenic. By electron microscopy, the ras- transformed cell lines showed nuclear abnormalities and loss of lamellar bodies. The ras-trans-formed lines were used as reference standards in the process of developing criteria for the selection of transformed colonies and a transformation assay suitable for mechanism studies on transformation by silica and other carcinogens.