Suppression of deregulated c-MYC expression in human colon carcinoma cells by chromosome 5 transfer.
Suppression of deregulated c-MYC expression in human colon carcinoma cells by chromosome 5 transfer.
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通过 5 号染色体转移抑制人结肠癌细胞中 c-MYC 表达失调。
DOI：
10.1073/pnas.89.4.1482
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发表时间：
1992
影响因子：
11.1
通讯作者：
Astrin,SM
中科院分区：
文献类型：
--
作者：
Rodriguez-Alfageme,C;Stanbridge,EJ;Astrin,SM
三分之二的散发性结肠癌表达c-myc原癌基因水平升高。此外，大多数结肠癌细胞株表现出结构性的MYC RNA和蛋白表达升高(比正常水平高10-40倍)，而不是对有丝分裂刺激的反应。间接免疫荧光已经被用来检测这些细胞系中的c-myc蛋白，这些细胞系与正常调节myc的细胞融合而产生的杂交细胞中，以及通过微细胞融合将正常的5号染色体拷贝转移到的癌细胞中。C-myc的非调控表达通过与正常调控myc的细胞融合而被抑制。此外，通过微细胞融合转移5号染色体可以抑制非调控表达。被抑制的细胞在裸鼠体内不再具有致瘤作用。转移的染色体丢失会导致致瘤表型的重新表达和MYC的结构性高表达。这些数据表明，5号染色体上的一个肿瘤抑制基因的功能对于MYC在至少一些结肠细胞中的调控表达是必要的。这种抑制基因的缺失会导致MYC表达失控，这是结肠癌亚群中肿瘤表型表达的必要事件，但很可能不是充分事件。
Two-thirds of sporadic colon carcinomas express elevated levels of the c-MYC protooncogene. In addition, most colon carcinoma cell lines show constitutive elevated expression (10- to 40-fold over normal) of MYC RNA and protein that is not modulated in response to a mitogenic stimulus. Indirect immunofluorescence has been used to detect c-MYC protein in such cell lines, in hybrid cells resulting from fusions of such lines with cells that regulate MYC normally, and in carcinoma cells to which a normal copy of chromosome 5 has been transferred by microcell fusion. The deregulated expression of c-MYC is suppressed by fusion with a cell that regulates MYC normally. In addition, transfer of chromosome 5 by microcell fusion results in suppression of deregulated expression. Suppressed cells are no longer tumorigenic in nude mice. Loss of the transferred chromosome results in reexpression of the tumorigenic phenotype and in constitutive elevated expression of MYC. These data indicate that function of a tumor-suppressor gene on chromosome 5 is necessary for the regulated expression of MYC in at least some colon cells. Loss of this suppressor results in deregulated MYC expression and is a necessary, but most likely not sufficient, event for the expression of the tumorigenic phenotype in a subset of colon carcinomas.