Clonal cosegregation of tumorigenicity with overexpression of c-myc and transforming growth factor alpha genes in chemically transformed rat liver epithelial cells.
Clonal cosegregation of tumorigenicity with overexpression of c-myc and transforming growth factor alpha genes in chemically transformed rat liver epithelial cells.
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发表时间：
1991-10
期刊：
影响因子：
11.2
通讯作者：
L. Lee;V. Raymond;Ming-Sound Tsao;Daiyoon Lee;H. Earp;J. Grisham
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作者：
L. Lee;V. Raymond;Ming-Sound Tsao;Daiyoon Lee;H. Earp;J. Grisham
在一系列16个克隆来源的转化肝上皮细胞系中，致瘤性与转化生长因子α (tgf - α)、表皮生长因子受体、c-myc、c-H-ras和c-K-ras基因的表达水平相关。通过将二倍体WB- f344 （WB）细胞反复暴露于n -甲基-n '-硝基-n -亚硝基胍产生的表型异质性群体中，建立了致瘤性从0%到97%不等的无性系。克隆系间基因表达与致瘤性的分离是通过比较克隆与野生型WB细胞基因表达的等级顺序来确定的。在所有转化的克隆中，只有c-myc基因的表达与致瘤性相关。tgf - α基因表达与所有克隆的致瘤性不相关，但在所有克隆中c-myc基因表达高于中位数水平（大于WB细胞表达水平的5倍）的克隆中，tgf - α基因表达与致瘤性高度相关。在c-myc基因表达水平低于WB细胞表达水平5倍的克隆中，即使tgf - α基因的高表达水平（高达WB细胞表达水平的60倍）也与致瘤性无关。同时过表达c-myc和tgf - α基因的克隆在所有克隆中均高于中位数水平，其致瘤性明显高于表达任一或两种基因均低于中位数水平的克隆。这些结果表明，过表达的c-myc和tgf - α基因在它们的致瘤性相关的合作。大多数高致瘤性克隆过度表达c-myc和tgf - α，也过度表达c-H-ras和/或c-K-ras基因；既不过度表达c-ras基因，也不过度表达c-myc和tgf - α基因的克隆不具有很强的致瘤性，而表达一个或两个c-ras基因（但不是同时表达c-myc和tgf - α）的克隆在中等范围内具有不同的致瘤性。
Tumorigenicity was correlated with levels of expression of the genes for transforming growth factor alpha (TGF-alpha), epidermal growth factor receptor, c-myc, c-H-ras, and c-K-ras in a series of 16 clonally derived transformed liver epithelial cell lines. The clonal lines, which varied in tumorigenicity from 0 to 97%, were established from a phenotypically heterogeneous population produced by repeated exposure of diploid WB-F344 (WB) cells to N-methyl-N'-nitro-N-nitrosoguanidine. Segregation of gene expression with tumorigenicity among clonal lines was determined by correlating rank orders of gene expression by clones relative to expression by wild-type WB cells. Only the expression of the c-myc gene correlated with tumorigenicity among all transformed clones. TGF-alpha gene expression was not correlated with tumorigenicity among all clones, but it was highly correlated with tumorigenicity among clones that expressed the c-myc gene above the median level for all clones (greater than 5-fold the level of expression by WB cells). Even high levels of expression of the TGF-alpha gene (up to 60-fold the level of expression by WB cells) were not correlated with tumorigenicity among the clones expressing the c-myc gene at levels less than 5-fold the level of expression by WB cells. Clones which simultaneously overexpressed both c-myc and TGF-alpha genes at levels above the median levels for all clones were significantly more tumorigenic than were clones which expressed either or both genes at lower than median levels. These results suggest that overexpressed c-myc and TGF-alpha genes cooperate in their association with tumorigenicity. Most of the highly tumorigenic clones that overexpressed c-myc and TGF-alpha also overexpressed the c-H-ras and/or the c-K-ras genes; clones that overexpressed neither of the c-ras genes nor the genes for c-myc and TGF-alpha were not very tumorigenic, while clones that expressed one or both c-ras genes (but not both c-myc and TGF-alpha) were variably tumorigenic over an intermediate range.