Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix
Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix
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DOI：
10.1046/j.1432-1033.2003.03440.x
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发表时间：
2003-03-01
期刊：
影响因子：
--
通讯作者：
Song, SY
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文献类型：
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作者：
Ishimi, Y;Okayasu, I;Song, SY
微小染色体维持蛋白（Mcm）2-7在真核生物DNA复制中起重要作用。一些报道已经表明Mcm蛋白作为癌细胞标记物在组织病理学诊断中的有用性。然而，它们在癌细胞中的表达模式和病理生理学意义仍有待澄清。我们比较了人宫颈癌细胞、SV 40转化的人成纤维细胞GM 00637和正常人成纤维细胞WI-38中Mcm蛋白的表达水平。在HeLa和GM细胞中检测到的所有蛋白质的平均水平是在WI-38细胞中发现的水平的6-10倍。在总细胞蛋白和染色质结合部分中均观察到这种增加。结果表明，Mcm 2 mRNA在HeLa细胞中的表达量约为WI-38细胞的4倍，Mcm 4、6和7蛋白在HeLa细胞中的合成量明显增加。来自人子宫颈的手术材料的免疫组织化学研究表明，Mcm 3和4在癌细胞中普遍表达。此外，Mcm 3和4表达的阳性率和水平似乎在癌细胞中高于子宫颈的正常增殖细胞和异型增生细胞，这表明它们可以是有用的标记物来区分这些细胞。
Minichromosome maintenance proteins (Mcm) 2-7 play essential roles in eukaryotic DNA replication. Several reports have indicated the usefulness of Mcm proteins as markers of cancer cells in histopathological diagnosis. However, their mode of expression and pathophysiological significance in cancer cells remain to be clarified. We compared the level of expression of Mcm proteins among human HeLa uterine cervical carcinoma cells, SV40-transformed human fibroblast GM00637 cells and normal human fibroblast WI-38 cells. All the proteins examined were detected in HeLa and GM cells at 6-10 times the level found in WI-38 cells on average. This increase was observed both in total cellular proteins and in the chromatin-bound fraction. Consistently, Mcm2 mRNA was enriched in HeLa cells to approximately four times the level in WI-38 cells, and the synthesis of Mcm4, 6 and 7 proteins was accelerated in HeLa cells. Immunohistochemical studies of surgical materials from human uterine cervix showed that Mcm3 and 4 are ubiquitously expressed in cancer cells. Further, the positive rate and level of Mcm3 and 4 expression appeared to be higher in cancer cells than in normal proliferating cells of the uterine cervix and dysplastic cells, suggesting that they can be useful markers to distinguish these cells.