Edmondson S W, Mossman B T
Department of Pathology, University of Vermont, College of Medicine, Burlington 05405-0068.
Carcinogenesis. 1991 Apr;12(4):679-84. doi: 10.1093/carcin/12.4.679.
Changes in keratin expression were documented in cultures of hamster tracheal epithelial (HTE) cells exposed to vitamin A (retinol 10(-6) M) and benzo[a]pyrene (B[a]P), two agents known to affect the differentiation of tracheal epithelial cells in vivo. Keratin protein patterns were determined after 10 days in culture in the presence and absence of B[a]P in order to determine whether the expression of these proteins was altered by this carcinogen. HTE cells maintained in the presence of vitamin A expressed four simple epithelial keratins (7,8,18 and 19) while vitamin A deficient HTE cells expressed four additional cytokeratins (5,6,14 and 17). No effect of B[a]P on keratin expression was observed in vitamin A treated cells. However, vitamin A deficient HTE cells exposed to B[a]P (0.05-10 micrograms/ml) demonstrated a decrease in the expression of the four differentiation-related keratins while the simple epithelial keratins appeared to be unaffected. These observations were verified at the RNA level employing Northern blot analysis using cDNA probes for human keratins 5,6 and 14. Results demonstrate that B[a]P alters the expression of differentiation-related genes, the cytokeratins, in cell types known to develop into tumors of the respiratory tract.
在暴露于维生素A（视黄醇10⁻⁶ M）和苯并[a]芘（B[a]P）的仓鼠气管上皮（HTE）细胞培养物中记录了角蛋白表达的变化，这两种物质在体内已知会影响气管上皮细胞的分化。为了确定这些蛋白质的表达是否被这种致癌物改变，在有和没有B[a]P的情况下培养10天后测定角蛋白蛋白模式。在维生素A存在下维持的HTE细胞表达四种简单上皮角蛋白（7、8、18和19），而缺乏维生素A的HTE细胞表达另外四种细胞角蛋白（5、6、14和17）。在维生素A处理的细胞中未观察到B[a]P对角蛋白表达的影响。然而，暴露于B[a]P（0.05 - 10微克/毫升）的缺乏维生素A的HTE细胞显示四种与分化相关的角蛋白的表达减少，而简单上皮角蛋白似乎未受影响。使用针对人角蛋白5、6和14的cDNA探针通过Northern印迹分析在RNA水平验证了这些观察结果。结果表明，B[a]P改变了已知会发展为呼吸道肿瘤的细胞类型中与分化相关的基因即细胞角蛋白的表达。
