Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype.
Alternative splicing variant of the hypoxia marker carbonic anhydrase IX expressed independently of hypoxia and tumour phenotype.
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DOI：
10.1038/sj.bjc.6604111
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发表时间：
2008-01-15
影响因子：
8.8
通讯作者：
Pastorek, J.
中科院分区：
文献类型：
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作者：
Barathova, M.;Takacova, M.;Holotnakova, T.;Gibadulinova, A.;Ohradanova, A.;Zatovicova, M.;Hulikova, A.;Kopacek, J.;Parkkila, S.;Supuran, C. T.;Pastorekova, S.;Pastorek, J.
CA IX是一种缺氧诱导的癌症相关碳酸酐酶同种型，其功能涉及pH控制和细胞粘附。在这里，我们描述了一种选择性剪接变异体的CA 9 mRNA，它不包含外显子8-9，并在肿瘤细胞中表达独立的缺氧。在不存在全长转录物的情况下，它在正常组织中也是可检测的，因此可以在基于检测缺氧和癌症相关的CA 9表达的预后研究中产生假阳性数据。剪接变体编码缺少催化结构域的C-末端部分的截短的CA IX蛋白。它显示出降低的催化活性，并且是细胞内的或分泌的。当过表达时，其降低全长CA IX蛋白酸化缺氧细胞的细胞外pH和结合碳酸酐酶抑制剂的能力。用剪接变体cDNA转染的HeLa细胞产生的球状体不会形成致密的核心，这表明它们无法适应缺氧应激。我们的数据表明，剪接变体可以在功能上干扰全长CA IX。这可能是相关的，特别是在轻度缺氧的条件下，当细胞不遭受严重的酸中毒，不需要过度的pH值控制。
CA IX is a hypoxia-induced, cancer-associated carbonic anhydrase isoform with functional involvement in pH control and cell adhesion. Here we describe an alternative splicing variant of the CA9 mRNA, which does not contain exons 8–9 and is expressed in tumour cells independently of hypoxia. It is also detectable in normal tissues in the absence of the full-length transcript and can therefore produce false-positive data in prognostic studies based on the detection of the hypoxia- and cancer-related CA9 expression. The splicing variant encodes a truncated CA IX protein lacking the C-terminal part of the catalytic domain. It shows diminished catalytic activity and is intracellular or secreted. When overexpressed, it reduces the capacity of the full-length CA IX protein to acidify extracellular pH of hypoxic cells and to bind carbonic anhydrase inhibitor. HeLa cells transfected with the splicing variant cDNA generate spheroids that do not form compact cores, suggesting that they fail to adapt to hypoxic stress. Our data indicate that the splicing variant can functionally interfere with the full-length CA IX. This might be relevant particularly under conditions of mild hypoxia, when the cells do not suffer from severe acidosis and do not need excessive pH control.
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影响因子：
8
作者：
Anderson, CJ;Hoare, SF;Keith, WN
通讯作者：
Keith, WN
影响因子：
7.3
作者：
Cecchi, A;Hulikova, A;Supuran, CT
通讯作者：
Supuran, CT
影响因子：
6.4
作者：
Chrastina, A;Závada, J;Pastoreková, S
通讯作者：
Pastoreková, S
影响因子：
64.8
作者：
Matter, N;Herrlich, P;König, H
通讯作者：
König, H
影响因子：
8.8
作者：
通讯作者：
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