|Budget Amount *help
¥3,400,000 (Direct Cost : ¥3,400,000)
Fiscal Year 2004 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2003 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2002 : ¥1,400,000 (Direct Cost : ¥1,400,000)
We have evaluated the relationship between chemo-sensitivity and gene expression profile in human gastrointestinal and hepatic cancer cells, by using cDNA microarray analysis, and analyzed the data by constructing relevance networks.
Pancreatic cancer is often unresectable at diagnosis, and chemotherapy using gemcitabine is now the standard treatment for advanced pancreatic cancer. Acquired resistance to gemcitabine resulting in therapeutic failure is often encountered. We sought to identify genes that determine gemcitabine resistance by evaluating the relationship between gene expression profiles and gemcitabine sensitivity to provide molecular targets for overcoming gemcitabine resistance.
Gemcitabine sensitivity was examined in six pancreatic cancer cell lines (Panc1, MIA-PaCa2, AsPC1, BxPC3, KPIN, Su86.86) using MTT assay. The gene expression profiles of these six cell lines were examined using cDNA microarray containing 10,000 genes. By comparing these results, 30 genes were identified as differentially expressed genes correlated with gemcitabine sensitivity.
In addition, we established gemcitabine-resistant cells by exposing MIA-PaCa-2 pancreatic cancer cells to long-term gemcitabine. We also compared the gene expression profiles between parental MIA-PaCa-2 and gemcitabine-resistant clone, and identified six overlapping genes (GPR3, CRYAB, RPS13, TNFSF6, PELO, STXBP3) correlated with gemcitabine sensitivity in both assays.
We are trying to analyze these 6 genes in specimen obtained by endoscopic ultrasonography guided fine needle aspiration biopsy and will examine relationship between the gene profiles and clinical outcome of chemotherapy treated by gemcitabine.