Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation.
Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation.
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有证据表明，家族性腺瘤性息肉病基因与 c-myc 调节中存在可互补缺陷的结肠癌亚型有关。
DOI：
10.1073/pnas.86.11.4264
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发表时间：
1989
影响因子：
11.1
通讯作者：
Astrin,SM
中科院分区：
文献类型：
--
作者：
Erisman,MD;Scott,JK;Astrin,SM
在 c-myc 基因座没有发生总体遗传变化的情况下，人类结直肠癌经常表达升高水平的 c-myc mRNA。为了检验这些肿瘤在调节 c-myc 表达所需的基因功能上存在缺陷的假设，我们将表现出正常 c-myc 调节的骨肉瘤细胞系与表达失调的 c-myc mRNA 水平的两种结肠癌细胞系融合。所有检查的杂交克隆中的 c-myc 转录物水平均正常，并且由促有丝分裂刺激物正常诱导。由于发现结肠癌细胞中的 c-myc mRNA 周转率与正常细胞中的相当，因此信息稳定性的增加不能解释转录物稳态水平的增加。我们的研究结果表明，反式作用调节因子功能的丧失是导致大部分结直肠癌中 c-myc 表达失调的原因。对原发性结直肠病变患者的肿瘤/正常组织对的限制性片段长度多态性分析表明，肿瘤中 c-myc 表达的失调与 5q 染色体上同线标记等位基因的频繁丢失相关。 19 个表达 c-myc mRNA 水平失调的肿瘤中有 9 个可检测到 5q 等位基因丢失，但在 8 个表达正常 c-myc RNA 水平的肿瘤中未检测到。 5q 染色体是已知含有家族性腺瘤性息肉病基因的区域，家族性腺瘤性息肉病是一种结肠癌的遗传倾向。这些发现与早期发现 c-myc 表达失调的肿瘤结肠分布与家族性息肉病相似，提供了证据表明家族性腺瘤性息肉病基因的功能丧失与 c-myc 表达失调的结直肠癌亚型有关。
Human colorectal carcinomas frequently express elevated levels of c-myc mRNA in the absence of a gross genetic change at the c-myc locus. To test the hypothesis that these tumors are defective in a gene function necessary for the regulation of c-myc expression, we fused an osteosarcoma cell line that exhibits normal c-myc regulation with two colon carcinoma cell lines that express deregulated levels of c-myc mRNA. The levels of c-myc transcripts in all of the hybrid clones examined were normal and were induced normally by a mitogenic stimulus. Since rates of c-myc mRNA turnover in the colon carcinoma cells were found to be comparable to those in normal cells, increased message stability cannot account for the increased steady-state levels of transcripts. Our findings suggest that loss of function of a trans-acting regulator is responsible for the deregulation of c-myc expression in a major fraction of colorectal carcinomas. Analysis of restriction fragment length polymorphisms in tumor/normal tissue pairs from patients with primary colorectal lesions indicated that deregulation of c-myc expression in the tumors is correlated with frequent loss of alleles of syntenic markers on chromosome 5q; allele loss on 5q could be detected in 9 of 19 tumors expressing deregulated levels of c-myc mRNA, but not in any of 8 tumors expressing normal levels of c-myc RNA. Chromosome 5q is the region known to contain the gene for familial adenomatous polyposis, an inherited predisposition to colon cancer. These findings, together with the earlier finding that the colonic distribution of tumors exhibiting deregulated c-myc expression is similar to that reported for familial polyposis, provide evidence that loss of function of the familial adenomatous polyposis gene is involved in a subset of colorectal cancers in which c-myc expression is deregulated.
影响因子：
4.3
作者：
H. Sambrook
通讯作者：
H. Sambrook