ANALYSIS OF GENE AMPLIFICATION AND OVEREXPRESSION IN HUMAN ESOPHAGEAL-CARCINOMA CELL-LINES
ANALYSIS OF GENE AMPLIFICATION AND OVEREXPRESSION IN HUMAN ESOPHAGEAL-CARCINOMA CELL-LINES
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DOI：
10.1002/ijc.2910580224
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发表时间：
1994-07-15
影响因子：
6.4
通讯作者：
FUKUMOTO, M
中科院分区：
文献类型：
--
作者：
KANDA, Y;NISHIYAMA, Y;FUKUMOTO, M
以c-myc、c-erbB、hst-1和cyClinD1为探针，通过Southern和Northern杂交，分析了23个人食管鳞癌组织细胞系的基因扩增/过表达。在5个高分化癌细胞系中发现c-myc基因扩增，且均伴有其他癌基因的共扩增。在3个细胞系中扩增出C-erbB基因。在9个细胞系中发现了hst-1和细胞周期蛋白d1的共同扩增，这两个基因均位于染色体11q13。它们的扩增无一例外都是同时进行的，而且扩增幅度相似。在建立细胞系的患者中，它们的扩增，而不是它们的过度表达，与不良的预后显著相关。虽然没有检测到hst-1基因的表达，但至少有1个被分析的基因在20个细胞系中过度表达，而在正常食道粘膜组织中却过度表达。然而，基因扩增并不一定伴随着相应基因的过度表达。细胞周期蛋白D1基因被认为是11q13扩增的靶基因，但在扩增11q13的细胞系中未检测到该基因的表达。这一结果表明，多个癌基因的扩增/过表达参与了食管癌的发生过程，c-myc基因的扩增与食管癌的分化程度有关。11q13扩增可能与细胞周期蛋白D1以外的关键癌基因有关。(C)1994年Wiley-Liss，Inc.
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 1 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. (C) 1994 Wiley-Liss, Inc.