Three Years Follow-up on a Colorectal Cancer Screening Program: A Prospective Cohort of 4,961 Asymptomatic Subjects

polyp number (WT-placebo=3±0.82,WT-DAPT=6.4±1.39).In addition, increased erosion of mucosal layer, infiltration of neutrophils and dysplasia were seen in the polyps of DAPT treated mice compared to placebo both induced with CAC.Western blot analysis indicated significantly decreased protein expression (in percent) of NICD (89.0±20.0),p53 (35.0±20.0),p21WAF1/Cip1 (57.0±9.0),Bax-1 (65.0±7.0) and caspase-3 (90.0±10.0)with Notch-1 inhibition compared to placebo group mice both induced with CAC.TUNEL staining showed decreased apoptosis in the colons of mice treated with DAPT (0.61±0.26) compared to placebo group (14.36±1.12)mice both induced with CAC.MMP-9 overexpression in HCT116 cells resulted in significantly increased protein expression of NICD, p53 and p21WAF1/Cip1 expression (2±0.05,2.8±0.3,4.5±0.05fold increase compared to vector transfection, respectively).Conclusion: MMP-9 via activation of Notch-1 signaling mediates p53 expression and modulates apoptosis, thereby acts as a tumor suppressor in CAC.