Laboratoire d'Ingénierie Moléculaire et Biochimie Pharmacologique, EA 3940, FR CNRS 2843, Université Paul Verlaine-Metz, Metz, France.
Clin Chem Lab Med. 2011 Oct;49(10):1707-14. doi: 10.1515/CCLM.2011.635. Epub 2011 Jun 16.
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 over-expression 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.
CDC25 splice variants mRNA levels were evaluated by semi-quantitative RT-PCR and by an original real-time RT-PCR assay.
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.
CDC25 splice variants could represent interesting potential breast cancer prognostic biomarkers.
CDC25 磷酸酶通过激活细胞周期依赖性激酶来控制细胞周期进程。三种 CDC25 同工型编码基因都经历了选择性剪接事件，这些事件产生了至少两种 CDC25A 变体和两种 CDC25B 和 CDC25C 变体。CDC25 的过表达在包括乳腺癌在内的几种类型的癌症中都有报道，并且通常与预后不良有关。然而，大多数先前的研究并未解决 CDC25 剪接变体的表达问题。在这里，我们评估了抗癌症药物敏感和耐药的乳腺癌细胞系中 CDC25 剪接转录本的表达，以鉴定潜在的乳腺癌生物标志物。
通过半定量 RT-PCR 和原始实时 RT-PCR 检测评估 CDC25 剪接变体的 mRNA 水平。
在研究的乳腺癌细胞系中，CDC25 剪接转录本表达存在差异。与它们的敏感对照细胞系 MCF-7 相比，VCREMS 和 DOXOR 乳腺癌细胞中 CDC25A2 变体的上调和 CDC25C5/C1 比值的增加与多药耐药有关。此外，VCREMS 耐药细胞中仅过度表达 CDC25B2 转录本，因此可能参与了某些类型的耐药性的发展。
CDC25 剪接变体可能代表有趣的潜在乳腺癌预后生物标志物。
