Sa1933 Overexpression of CD44v9 in Gastric Cancer Cells Confers Resistance to Trastuzumab by Inducing Antioxidant Enzymes That Inhibit Tumor Cell Death Induced by Oxidative Stress

Abstract

Background and aim: Aberrant DNA methylation plays critical roles in the development of colorectal cancers (CRCs). Laterally spreading tumors (LSTs) are generally defined as lesions greater than 10 mm in diameter with a low vertical axis that extend laterally along the luminal wall. Those flat lesions are thought to be less invasive because they are likely to be found in the adenoma stage or intramucosal CRCs. On the other hand, a subset of CRCs are known to develop from nonpolypoid lesions and the nonpolypoid submucosal invasive CRCs were smaller than did the polypoid cancers. We aimed to identify DNA methylation changes, which are associated with growth pattern and invasiveness of colorectal tumors. Methods: Methylated CpG island amplification coupled with CpG island microarray (MCAM) analysis was carried out to screen for differentially methylated genes between large (≥20 mm in diameter) noninvasive tumors (NTs) and small (<20 mm in diameter) invasive tumors (ITs). Bisulfite pyrosequencing was used to analyze methylation of the NTSR1 gene. Colony formation assay, MTT assay and Matrigel invasion assays were carried out to analyze the function of NTSR1. Results: MCAM analysis in large NTs (n = 3) and small ITs (n = 3) identified elevated levels of methylation of NTSR1 in large ITs. Quantitative bisulfite pyrosequencing analysis in a large set of clinical samples (large IT, n = 78; small IT, n = 13; large NT, n = 28; small NT, n = 96; normal colon, n= 66) revealed that NTSR1