Differential expression of CDC25 phosphatases splice variants in human breast cancer cells
Differential expression of CDC25 phosphatases splice variants in human breast cancer cells
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DOI：
10.1515/cclm.2011.635
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发表时间：
2011-10-01
影响因子：
6.8
通讯作者：
Bagrel, Denyse
中科院分区：
文献类型：
--
作者：
Albert, Helene;Santos, Susana;Bagrel, Denyse
背景：CDC25磷酸酶通过激活细胞周期蛋白依赖激酶来控制细胞周期进程。编码基因的三种CDC25同种异构体被提交到可选择的剪接事件中，产生CDC25A的至少两个变体和CDC25B和CDC25C的五个变体。据报道，CDC25在包括乳腺癌在内的几种类型的癌症中过表达，并且通常与不良预后相关。然而，大多数先前的研究并没有涉及CDC25剪接变异体的表达。在这里，我们评估了CDC25剪接转录物在抗癌药物敏感和耐药乳腺癌细胞系中的表达，以确定潜在的乳腺癌生物标志物。方法：采用半定量RT-PCR和实时RT-PCR检测CDC25剪接变异体mRNA水平。结果：CDC25剪接转录物在乳腺癌细胞系中存在差异表达。与敏感的对应细胞系MCF-7相比，CDC25A2变异的上调和CDC25C5/C1比值的增加与VCREMS和DOXOR乳腺癌细胞的多药耐药有关。此外，CDC25B2转录本仅在VCREMS耐药细胞中过表达，因此可能参与某些类型耐药的发展。结论：CDC25剪接变异可能代表有趣的潜在乳腺癌预后生物标志物。
Background: CDC25 phosphatases control cell cycle progression by activating cyclin dependent kinases. The three CDC25 isoforms encoding genes are submitted to alternative splicing events which generate at least two variants for CDC25A and five for both CDC25B and CDC25C. An overexpression of CDC25 was reported in several types of cancer, including breast cancer, and is often associated with a poor prognosis. Nevertheless, most of the previous studies did not address the expression of CDC25 splice variants. Here, we evaluated CDC25 spliced transcripts expression in anti-cancerous drug-sensitive and resistant breast cancer cell lines in order to identify potential breast cancer biomarkers.Methods: CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original realtime RT-PCR assay.Results: CDC25 spliced transcripts are differentially expressed in the breast cancer cell lines studied. An up-regulation of CDC25A2 variant and an increase of the CDC25C5/C1 ratio are associated to the multidrug-resistance in VCREMS and DOXOR breast cancer cells, compared to their sensitive counterpart cell line MCF-7. Additionally, CDC25B2 transcript is exclusively over-expressed in VCREMS resistant cells and could therefore be involved in the development of certain type of drug resistance.Conclusions: CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.