Expression and regulation of MIM (Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines
Expression and regulation of MIM (Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines
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DOI：
10.1016/j.canlet.2004.05.002
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发表时间：
2004-11-25
期刊：
影响因子：
9.7
通讯作者：
Jackson, P
中科院分区：
文献类型：
--
作者：
Nixdorf, S;Grimm, MO;Jackson, P
已经提出由染色体8q24.1上的MIM（Missing In Metastasis）基因编码的356个氨基酸的蛋白是膀胱癌转移抑制因子。最近，Machesky和同事[Biochem.J.371（2003）463]鉴定了MIM-B，一种759个氨基酸的蛋白质，其C-末端356个氨基酸几乎与MIM相同。重要的是，在膀胱癌中MIM的研究中使用的PCR引物和北方印迹探针不能区分MIM或MIM-B的特异性序列，因此这两种蛋白质对膀胱癌的重要性仍然不清楚。我们已经使用特异于MIM或MIM-B的引物序列来探索MIM和MIM-B对膀胱癌细胞行为的可能的功能意义。我们已经比较了MIM和MIM-B的mRNA水平在非致瘤性，非侵入性，转化的尿路上皮细胞系与15个膀胱癌细胞系的不同的体外侵袭能力，以及在5个细胞系克隆分离的BL 17/2膀胱肿瘤细胞系，其在体外和体内的侵袭能力已被确定。MIM和MIM-B mRNA水平在细胞系之间变化很大。MIM和MIM-B的下调发生在6/15（40%）株系中，但显示下调的株系在MIM和MIM-B之间不同。BL 17/2中降低的MIM和MIM-B水平在2/5（40%）亚系（MIM和MIM-B）中进一步降低。重要的是，MIM或MIM-B表达与体内或体外侵袭行为之间没有关联。用5-氮杂-2-脱氧胞苷处理代表性细胞系未能诱导MIM或MIM-B表达。此外，MIM或MIM-B mRNA水平与p53功能状态之间没有关联。我们的数据表明，MIM和/或MIM-B表达的下调可以发生在膀胱癌细胞系中，但与增加的侵袭行为无关。我们的数据还表明，在MIM和MIM-B mRNA水平降低的细胞系中，下调不太可能是由于启动子超甲基化或p53功能丧失。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
It has been proposed that a 356 amino acid protein encoded by the MIM (Missing In Metastasis) gene on Chromosome 8q24.1, is a bladder cancer metastasis suppressor. Recently, Machesky and colleagues [Biochem. J. 371 (2003) 463] identified MIM-B, a 759 amino acid protein, of which the C-terminal 356 amino acids are almost identical to MIM. Importantly, PCR primers and Northern Blotting probes used in the studies of MIM in bladder cancer did not distinguish between sequences specific for MIM or MIM-B, thus the importance of either protein to bladder cancer remains unclear. We have used primer sequences specific for either MIM or MIM-B to explore the possible functional significance of MIM and MIM-B to bladder cancer cell behaviour. We have compared MIM and MIM-B mRNA levels in a non-tumourigenic, non-invasive, transformed uro-epithelial cell line versus 15 bladder cancer cell lines of differing in vitro invasive abilities, as well as in five cell lines clonally isolated from the BL17/2 bladder tumour cell line, whose in vitro and in vivo invasive abilities have been determined. MIMand MIM-B mRNA levels varied widely between cell lines. Down-regulation of MIM and MIM-B occurred in 6/15 (40%) lines but lines showing down-regulation differed between MIM and MIM-B. Reduced levels of MIM and MIM-B in BL17/2 were further reduced in 2/5 (40%) sublines (MIM and MIM-B). Importantly, there was no association between MIM or MIM-B expression and invasive behaviour in vivo or in vitro. Treatment of representative cell lines with 5-aza-2-deoxycytidine failed to induce MIM or MIM-B expression. Furthermore, there was no association between MIM or MIM-B mRNA levels and p53 functional status. Our data indicate that down-regulation of MIM and/or MIM-B expression can occur in bladder cancer cell lines but is not associated with increased invasive behaviour. Our data also suggest that in those cell lines with reduced levels of MIM and MIM-B mRNA, down-regulation is unlikely to be due to promoter hypermethylation or loss of p53 function. (C) 2004 Elsevier Ireland Ltd. All rights reserved.