Expression profiles of pancreatic cancer cell lines infected with antisense K- ras-expressing adenoviral vector

Abstract

The point mutations of the K- ras gene occur in as high as 70–90% of the cases with adenocarcinoma of the pancreas and apparently represent one of the key and early events in the carcinogenesis. However, the specific influence of the K- ras activation on global gene expression profiles in pancreatic cancer cells has not been elucidated. In this study, to promote elucidation of the K- ras-triggered molecular cascade(s) in pancreatic cancer, four pancreatic cancer cell lines with K- ras point mutations were infected with an adenovirus vector expressing an antisense K- ras RNA (AxCA-AS), and the change of gene expression was analyzed by oligonucleotide-based microarrays containing 12,626 genes. Among the genes showing more than 2-fold differences in the expression levels between the control- and antisense-K- ras-transduced cells, 7 genes were commonly up-regulated and 4 genes were commonly down-regulated in three or all of the four pancreatic cancer cell lines transduced with AxCA-AS. The altered gene expression levels observed by microarrays were confirmed by real-time RT-PCR methods. Then, the expression of the 4 down-regulated genes was examined in the untransduced surgical specimens of pancreatic cancer. The G-protein coupled receptor RE2 and phenylethanolamine N-methyltransferase had negligible expression levels in all pancreatic cancers, whereas the syntaxin 1A and p120 catenin isoform were significantly up-regulated in pancreatic cancers containing K- ras mutations compared with a pancreatic cancer with wild type K- ras gene. The transcriptional regulation of those genes may be a part of the molecular cascades triggered by K- ras activation leading to the development and/or progression of pancreatic cancer.