unlike pancreatic cancer cells pancreatic cancer associated fibroblasts display minimal gene induction after 5-aza-2′-deoxycytidine与胰腺癌细胞胰腺癌相关成纤维细胞显示最小基因诱导后5-aza-2u2032脱氧胞苷.pdf

Unlike Pancreatic Cancer Cells Pancreatic Cancer Associated Fibroblasts Display Minimal Gene Induction after 5-Aza-29-Deoxycytidine 1. 1. 1 1 1 1 Jun Yu , Kimberly Walter , Noriyuki Omura , Seung-Mo Hong , Angela Young , Ang Li , Audrey Vincent1, Michael Goggins1,2,3* 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The John Hopkins Medical Institutions, Baltimore, Maryland, United States of America, 2 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, The John Hopkins Medical Institutions, Baltimore, Maryland, United States of America, 3 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The John Hopkins Medical Institutions, Baltimore, Maryland, United States of America Abstract Purpose: Cancer associated stromal fibroblasts (CAFs) undergo transcriptional and phenotypic changes that contribute to tumor progression, but the mechanisms responsible for these changes are not well understood. Aberrant DNA methylation is an important cause of transcriptional alterations in cancer cells but it is not known how important DNA methylation alterations are to CAF behavior. Experimental Design: We used Affymetrix exon arrays to compare genes induced by the DNA methylation inhibitor 5-aza- dC in cultured pancreatic cancer associated fibroblasts, pancreatic control fibroblasts and pancreatic cancer cell lines. Results: We found that pancreatic CAFs and control pancreatic fibroblasts were less responsive to 5-aza-dC-mediated gene reactivation than pancreatic cancer cells (mean+/ 2SD of genes induced $5-fold was 9610 genes in 10 pancreatic CAF cultures, 17614 genes in 3 control pancreatic fibroblast cultures, and 134685 genes in 4 pancreatic cancer cell lin