Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells
Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells
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DOI：
10.1007/s00432-009-0679-0
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发表时间：
2010-03-01
影响因子：
3.6
通讯作者：
Sueoka, Eisaburo
中科院分区：
文献类型：
--
作者：
Komiya, Kazutoshi;Sueoka-Aragane, Naoko;Sueoka, Eisaburo
Mina53直接由c-Myc诱导表达，在多种癌症中过表达，在细胞生长中起重要作用。为了阐明Mina53在肺癌中的作用，我们研究了它在人肺癌组织和各种肺癌细胞系中的表达。使用肺癌细胞系、正常人支气管上皮细胞和肺癌组织，采用实时RT-PCR、western blotting和免疫组化检测Mina53的表达。用转染Mina53的NIH/3T3细胞，通过软琼脂集落形成实验和裸鼠致瘤性评价Mina53的生物学效应。采用cDNA芯片分析Mina53对基因的改变，用实时RT-PCR方法用Mina53表达质粒或Mina53 shrna转染NIH/3T3细胞进行验证。我们观察到62%的患者在肺癌的早期临床阶段就证实了Mina53的过表达。性别、吸烟状况或组织学类型的差异无统计学意义。在NIH/3T3细胞中强制表达Mina53诱导细胞转化，转染Mina53的NIH/3T3克隆在裸鼠体内产生肿瘤，表明Mina53具有致瘤潜能。cDNA微阵列显示，254个基因在mina53转染的NIH/3T3克隆中表达改变。Mina53调节几个与细胞粘附和代谢相关的基因，这些基因也被报道由c-Myc调节。受Mina53调控而不受c-Myc调控的基因包括细胞因子/生长因子相关基因，如EGFR、IL-6和HGF。我们的研究结果表明，Mina53在癌症发生中起着重要作用，可能是癌症预防的靶点。
Mina53, whose expression is directly induced by c-Myc, is overexpressed in various cancers and plays an important role in cell growth. To clarify the involvement of Mina53 in lung cancers, we investigated its expression in human lung cancer tissues as well as in various lung cancer cell lines.Mina53 expression was determined by real-time RT-PCR, western blotting, and immunohistochemistry using lung cancer cell lines, normal human bronchial epithelial cells, and lung cancer tissues. Biological effects of Mina53 were evaluated by soft agar colony formation assay and tumorigenicity in nude mice using Mina53-transfected NIH/3T3 cells. cDNA microarray analysis was performed to determine the gene alteration by Mina53 and confirmation was made using real-time RT-PCR with mina53 expression plasmid or mina53 shRNA-transfected NIH/3T3 cells.We observed that 62% of patients evidenced overexpression of Mina53 from the early clinical stages of lung cancer. Differences according to gender, smoking status, or histologic type were not statistically significant. Forced expression of Mina53 in NIH/3T3 cells induced cell transformation, and mina53-transfected NIH/3T3 clones produced tumors in nude mice, demonstrating that Mina53 has oncogenic potential. cDNA microarray revealed that 254 genes had altered expression in a mina53-transfected NIH/3T3 clone. Mina53 regulates several genes related to cell adhesion and metabolism, which have also been reported to be regulated by c-Myc. Genes regulated by Mina53, but not by c-Myc included cytokine/growth factor related genes such as EGFR, IL-6, and HGF.Our results suggest that Mina53 plays an important role in carcinogenesis and may be a target for cancer prevention.