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首页> 外文期刊>Digestive Diseases and Sciences >Human Colon Cancer Cells Deficient in DCC Produce Abnormal Transcripts in Progression of Carcinogenesis
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Human Colon Cancer Cells Deficient in DCC Produce Abnormal Transcripts in Progression of Carcinogenesis

机译:缺乏DCC的人结肠癌细胞在癌变过程中产生异常转录本

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Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may be superior to lymph node status in predicting patient survival for intermediate stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting DCC would be ideal as a prognostic indicator. DCC is an alternatively spliced molecule; thus, reliability of a PCR test for DCC will depend on amplifying only those regions of the molecule that are lost in the progression of colon cancer. For this reason, we studied a colon cancer cell line model at different stages of tumor progression to determine the alternative splice pattern for DCC. A commercially available colon cancer cell line system at different stages of tumor progression was used to identify which DCC exons are lost by western blot analysis, PCR, and RT-PCR techniques. Colon cancers express abnormal DCC transcripts. The proximal and distal exons are present (exons 2 and 28–29). Exons located in the center of the molecule are absent (6–7 and 18–23). This correlated to DCC protein loss in the cell lines. For clinical utility as a disease marker, exons in the middle portion of the DCC molecule that are spliced out should be utilized. Amplification of the proximal and distal regions will result in falsely concluding that DCC is present when its protein product is not expressed.
机译:结肠癌(DCC)中缺失的肿瘤抑制因子的表达丧失在预测中期结肠癌患者生存率方面可能优于淋巴结状态。基于聚合酶链反应(PCR)的DCC检测方法将是理想的预后指标。 DCC是一个选择性剪​​接的分子;因此,用于DCC的PCR测试的可靠性将取决于仅扩增在结肠癌进展过程中丢失的分子区域。因此,我们研究了肿瘤进展不同阶段的结肠癌细胞系模型,以确定DCC的替代剪接模式。通过western印迹分析,PCR和RT-PCR技术,使用市售的结肠癌细胞系系统在肿瘤进展的不同阶段来鉴定哪些DCC外显子丢失。结肠癌表达异常的DCC转录本。存在近端和远端外显子(外显子2和28-29)。位于分子中心的外显子不存在(6-7和18-23)。这与细胞系中DCC蛋白的损失有关。为了在临床上用作疾病标记物,应利用DCC分子中间部分的外显子剪接。近端和远端区域的扩增将导致错误地得出结论,当未表达其蛋白质产物时,DCC存在。

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