Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative coloredtal tumorigenesis (Cancer Cell, 2010, 18:135-146)

報告日期: 2011/04/01
報告時間: 15:10/16:00
報告學生: 陳雅均
講評老師: 蔣輯武
附件下載:

Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0401-1.pdf

Ink4a/Arf and Oncogene-Induced Senescence Prevent Tumor Progression during Alternative Colorectal Tumorigenesis
 
SourceCancer Cell 2010 ; 18(2):135-46.
AuthorsMoritz Bennecke, Lydia Kriegl, Monther Bajbouj, Kristin Retzlaff, Sylvie Robine, Andreas Jung, Melek C. Arkan, Thomas Kirchner, and Florian R. Greten.
Commentator:蔣輯武老師
Speaker:陳雅均
 
Abstract:
Backgroud: Mutation of K-ras have been detected as the earliest genetic alterations in serrated lesions. In addition, this is different in mutations of adenomatous polyposis coli (APC) gene, which have been reported to be the most common acquired genetic change in sporadic colon cancer. Oncogenic K-ras mediated Erk activation induced senescence and impaired malignant tumor progression.
Objective: To investigate the enterocyte specific expression of oncogenic K-ras in mice (K-rasG12Dint) can induce colonic lesions.
Results: At firstly, the author found that the expression of K-rasG12D in mice was sufficient to promote colonic tumor growth. The K-rasG12Dint mice exhibit oncogene- induced senescence (OIS), which was further supported by upregulation of p16ink4a in colon epithelium. They observed that further knockout Ink4a/Arf in this mice can promote cell proliferation and tumor progression. Interesting, the morphological and molecular alterations in the cancer of K-rasG12Dint/Ink4a/Arf -/- mice resemble to human K-ras mutated serrated tumors.
Conclusion: This study provides evidence that activation of the RAS-RAF-MEK-ERK cascade may be the initiating event in serrated colorectal tumors.
 
Reference:
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