Kanda Y, Nishiyama Y, Shimada Y, Imamura M, Nomura H, Hiai H, Fukumoto M
Department of Pathology, Faculty of Medicine, Kyoto University, Japan.
Int J Cancer. 1994 Jul 15;58(2):291-7. doi: 10.1002/ijc.2910580224.
Gene amplification/overexpression was analyzed in 23 cell lines derived from human esophageal squamous-cell-carcinoma tissues by Southern and Northern hybridizations to c-myc, c-erbB, hst-1 and cyclin-D1 probes. Amplification of the c-myc gene was observed in 5 cell lines derived from well-differentiated carcinomas and all of them were accompanied by co-amplification of other examined oncogenes. The c-erbB gene was amplified in 3 cell lines. Co-amplification of hst-1 and cyclin D1, both of which are located in chromosome 11q13, was found in 9 cell lines. Without exception their amplification was simultaneous and the magnitudes were similar. Their amplification, but not their overexpression, was significantly correlated with poor prognosis in patients from whom the cell lines were established. While hst-1-gene expression was not detected, at least 1 of the genes analyzed was overexpressed in 20 cell lines vs. its expression in normal esophageal mucosal tissues. However, gene amplification was not necessarily accompanied by overexpression of the corresponding genes. Expression of the cyclin D1 gene, which has been assumed to be a target gene for 11q13 amplification, was not detected in one particular cell line with amplification of 11q13. These results suggest that the amplification/overexpression of more than I oncogene is involved in the carcinogenic process of esophageal carcinoma and that c-myc-gene amplification is associated with a well-differentiated subtype. There remains a possibility that key oncogenes other than cyclin D1 are involved in 11q13 amplification.
通过对源自人食管鳞状细胞癌组织的23个细胞系进行Southern杂交和Northern杂交，以c-myc、c-erbB、hst-1和细胞周期蛋白D1探针分析基因扩增/过表达情况。在源自高分化癌的5个细胞系中观察到c-myc基因扩增，并且所有这些细胞系均伴有其他检测的癌基因的共扩增。c-erbB基因在3个细胞系中扩增。在9个细胞系中发现位于染色体11q13的hst-1和细胞周期蛋白D1共扩增。无一例外，它们的扩增是同时发生的，且幅度相似。它们的扩增而非过表达与建立细胞系的患者的不良预后显著相关。虽然未检测到hst-1基因表达，但与正常食管黏膜组织相比，在20个细胞系中至少有1个分析的基因过表达。然而，基因扩增不一定伴随着相应基因的过表达。在一个特定的11q13扩增的细胞系中未检测到被认为是11q13扩增靶基因的细胞周期蛋白D1基因的表达。这些结果表明，一种以上癌基因的扩增/过表达参与食管癌的致癌过程，并且c-myc基因扩增与高分化亚型相关。仍有可能除细胞周期蛋白D1外的关键癌基因参与11q13扩增。
