Cancer-associated expression of minichromosome maintenance 3 gene in several human cancers and its involvement in tumorigenesis
Cancer-associated expression of minichromosome maintenance 3 gene in several human cancers and its involvement in tumorigenesis
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DOI：
10.1158/1078-0432.ccr-04-1029
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发表时间：
2004-12-15
影响因子：
11.5
通讯作者：
Kim, JW
中科院分区：
文献类型：
--
作者：
Ha, SA;Shin, SM;Kim, JW
目的：本研究的目的是鉴定一个与肿瘤相关的基因，评估其在肿瘤诊断中的潜在应用，并描述其与人类肿瘤发生相关的功能。实验设计：我们采用差异显示逆转录-PCR方法，对正常宫颈、宫颈癌和转移组织以及宫颈癌细胞系进行鉴定，以确定在肿瘤中过表达的基因。我们发现了一种微小染色体维持3（MCM 3）基因，该基因在多种人类癌症中过表达，包括白血病、淋巴瘤、宫颈癌、结肠癌、肺癌、胃癌、肾癌和乳腺癌以及恶性黑色素瘤。Western blot和免疫组化分析也显示，MCM 3蛋白在大多数检测的人类癌组织中升高。我们比较了MCM 3蛋白在人类癌症中的表达水平与传统的增殖标记物Ki-67和增殖细胞核抗原。MCM 3抗体对多种人类癌症的特异性最高，而增殖细胞核抗原的特异性相对较低，Ki-67未能检测到几种人类癌症。在正常细胞和癌细胞中，在血清饥饿下检测MCM 3蛋白水平的下调。有趣的是，MCM 3蛋白在MCF-7乳腺癌细胞中甚至在血清饥饿后长达96小时都是稳定的，而它在正常BJ成纤维细胞中逐渐降解。结论：MCM 3表达水平的测定有助于肿瘤诊断中对多种人类恶性肿瘤的评估，MCM 3参与多种人类肿瘤的发生。
Purpose: The purpose of our study was to identify an unique gene that shows cancer-associated expression, evaluates its potential usefulness in cancer diagnosis, and characterizes its function related to human carcinogenesis.Experimental Design: We used the differential display reverse transcription-PCR method with normal cervical, cervical cancer and metastatic tissues, and cervical cancer cell line to identify genes overexpressed in cancers.Results: We identified a minichromosome maintenance 3 (MCM3) gene that was overexpressed in various human cancers, including leukemia, lymphoma, and carcinomas of the uterine cervix, colon, lung, stomach, kidney and breast, and malignant melanoma. Western blot and immunohistochemical analyses also revealed that MCM3 protein was elevated in most of human cancer tissues tested. We compared the MCM3 protein expression levels in human cancers with conventional proliferation markers, Ki-67 and proliferating cell nuclear antigen. MCM3 antibody was the most specific for multiple human cancers, whereas proliferating cell nuclear antigen was relatively less effective in specificity, and Ki-67 failed to detect several human cancers. The down-regulation of MCM3 protein level was examined under serum starvation in both normal and cancer cells. Interestingly, MCM3 protein was stable in MCF-7 breast cancer cells even up to 96 hours after serum starvation, whereas it was gradually degraded in normal BJ fibroblast cells. Nude mice who received injections of HEK 293 cells stably transfected with MCM3 formed tumors in 6 weeks.Conclusions: Our study indicates that determination of MCM3 expression level will facilitate the assessment of many different human malignancies in tumor diagnosis, and MCM3 is involved in multiple types of human carcinogenesis.