RRC ID |
1470
|
著者 |
Nakatsu N, Yoshida Y, Yamazaki K, Nakamura T, Dan S, Fukui Y, Yamori T.
|
タイトル |
Chemosensitivity profile of cancer cell lines and identification of genes determining chemosensitivity by an integrated bioinformatical approach using cDNA arrays.
|
ジャーナル |
Mol Cancer Ther
|
Abstract |
We have established a panel of 45 human cancer cell lines (JFCR-45) to explore genes that determine the chemosensitivity of these cell lines to anticancer drugs. JFCR-45 comprises cancer cell lines derived from tumors of three different organs: breast, liver, and stomach. The inclusion of cell lines derived from gastric and hepatic cancers is a major point of novelty of this study. We determined the concentration of 53 anticancer drugs that could induce 50% growth inhibition (GI50) in each cell line. Cluster analysis using the GI50s indicated that JFCR-45 could allow classification of the drugs based on their modes of action, which coincides with previous findings in NCI-60 and JFCR-39. We next investigated gene expression in JFCR-45 and developed an integrated database of chemosensitivity and gene expression in this panel of cell lines. We applied a correlation analysis between gene expression profiles and chemosensitivity profiles, which revealed many candidate genes related to the sensitivity of cancer cells to anticancer drugs. To identify genes that directly determine chemosensitivity, we further tested the ability of these candidate genes to alter sensitivity to anticancer drugs after individually overexpressing each gene in human fibrosarcoma HT1080. We observed that transfection of HT1080 cells with the HSPA1A and JUN genes actually enhanced the sensitivity to mitomycin C, suggesting the direct participation of these genes in mitomycin C sensitivity. These results suggest that an integrated bioinformatical approach using chemosensitivity and gene expression profiling is useful for the identification of genes determining chemosensitivity of cancer cells.
|
巻・号 |
4(3)
|
ページ |
399-412
|
公開日 |
2005-3-1
|
DOI |
10.1158/1535-7163.MCT-04-0234
|
PII |
4/3/399
|
PMID |
15767549
|
MeSH |
Antineoplastic Agents / pharmacology*
Camptothecin / analogs & derivatives*
Camptothecin / pharmacology
Cell Line, Tumor
Cluster Analysis
Computational Biology / methods*
DNA, Complementary / metabolism
Databases as Topic
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Gene Expression Profiling / methods*
Gene Expression Regulation, Neoplastic*
Humans
Irinotecan
Mitomycin / pharmacology
Oligonucleotide Array Sequence Analysis / methods*
Paclitaxel / pharmacology
Phylogeny
Sensitivity and Specificity
Tissue Distribution
Transfection
Vinblastine / analogs & derivatives*
Vinblastine / pharmacology
Vinorelbine
|
IF |
5.615
|
引用数 |
52
|
WOS 分野
|
ONCOLOGY
|
リソース情報 |
ヒト・動物細胞 |
GCIY(RCB0555)
GT3TKB(RCB0885)
HGC-27(RCB0500)
HuH-6(RCB1367)
RBE(RCB1292)
SSP-25(RCB1293)
HuL-1 |