SLIT2 axon guidance molecule is frequently inactivated in colorectal cancer and suppresses growth of colorectal carcinoma cells.
作者： Eamonn R Maher , Farida Latif , Dion Morton , Ashraf Dallol
DOI:
关键词: Demethylating agent 、 Mouse model of colorectal and intestinal cancer 、 Tumor M2-PK 、 DNA methylation 、 Biology 、 Deleted in Colorectal Cancer 、 Candidate Tumor Suppressor Gene 、 Colorectal cancer 、 Cancer research 、 Tumor suppressor gene
摘要: We have shown recently that SLIT2 has tumor suppressor activity and it is epigenetically silenced in >40% of lung breast tumors. In this study, we analyzed the methylation status primary colorectal cancers matching normal mucosa. promoter region was found 23 (72%) 32 cancers. contrast, mucosa from same patients exhibited significantly lower levels hypermethylation. reversed expression restored by treating cell lines with demethylating agent 5-aza-2-deoxycytidine. Loss heterozygosity at D4S1546 marker, which maps within 100 kb gene, observed 39% methylated Furthermore, epigenetic silencing independent ROBO1/p16/RASSF1A The presence also K-RAS mutations. Ectopic diminished ability to form colonies two lines. addition, conditioned medium SLIT2-transfected COS-7 cells reduced growth induced apoptosis SW48 line. conclusion, an excellent candidate gene for cancer.
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