Gene expression profiling in human lung fibroblast following cadmium exposure
FOOD AND CHEMICAL TOXICOLOGY
Authors: Li, Guang-Yong; Kim, Mingoo; Kim, Ju-Han; Lee, Mi-Ock; Chung, Jin-Ho; Lee, Byung-Hoon
Abstract
Cadmium is a naturally occurring metallic element with food and smoking being the main sources of exposure in the non-occupationally exposed population. Chronic exposure to cadmium leads to tumors in a number of tissues including lung. In the present study we investigated genes whose expression is modified by Cd exposure in human lung fibroblast W138-VA13 cells. We employed a cDNA microarray hybridization method to identify changes in the gene expression profile. Thirty five genes were identified as cadmium-responsive. Their level of expression differed significantly from controls (significance analysis of microarray; SAM, q < 5%). The largest groups of gene products affected by cadmium exposure were those involved in cell cycle, immunity and defense, nucleoside metabolism and signal transduction. Repressed expression of E2f1, Tubb and Actg2 following cadmium exposure may contribute to the cell cycle arrest. Down-regulation of Enol indicates a potential for causing protooncogene expression and possibly for cadmium-induced carcinogenicity. These results may contribute to better understand the toxic mechanism of cadmium toxicity. Moreover, the gene expression profile of cadmium could provide potential biomarkers for cadmium exposure. (c) 2007 Elsevier Ltd. All rights reserved.
Expression microarray analysis reveals genes associated with in vitro resistance to cisplatin in a cell line model
ACTA ONCOLOGICA
Authors: Watson, Mark B.; Lind, Michael J.; Smith, Laura; Drew, Philip J.; Cawkwell, Lynn
Abstract
We aimed to investigate the mechanisms of cisplatin resistance using an in vitro cancer model. A derivative breast cancer cell line (MCF-7CR) was established which demonstrated significant resistance to cisplatin at clinically relevant low concentrations compared to the MCF-7 parental cell line. Expression microarray analysis was used to identify targets from a 3k cancer-related oligonucleotide platform which were differentially expressed between the derivative and parental cell lines. Real-time quantitative PCR was used to confirm the difference in expression of a subset of genes which demonstrated significant up- or down-regulation. Using expression microarray analysis a total of 28 genes were identified to be differentially expressed (by at least 2-fold) between the MCF-7 and MCF-7CR cells. Real-time quantitative PCR expression analysis confirmed the differential expression of a selection of these genes (ACTG2, ARHD, CTSL, GSTM3, GSTM4 and EHF) between the two cell lines. An in vitro model of cisplatin resistance has been established and expression microarray analysis revealed 28 genes which may be associated with cisplatin resistance.