Screeing The Differential Expression Of Adriamycin-resistance Related Gene To Breast Cancer By CDNA Microarray

BACKGROUND:Chemotherapy is one of the most important treatment of breast cancer.Chemoresistance is a major clinical problem in the treatment of human malignancy.Because of heterogeneity,breast tumors are diverse in their responsiveness to chemotherapy.It's very necessary to establish a method and select indicators for predicting efficacy of anticancer drugs for individual patients.OBJECTIVE:To study the gene differential expression of adriamycinresistant breast cancer cell line MCF-7/adr compared with its parent cell MCF-7 and discuss the relationship between gene differential expression and drug-resistance.METHODS:The drug sensitivities of MCF-7/adr and MCF-7 cell lines to ADM(adriamycin)were examined by MTT assay.Then a cDNA microamay representing 14,755 genes was used to analyze expression profiles of the two breast cancer cell lines.RESULTS:The differences of chemosensitivity to adriamycin were showed between MCF-7 and MCF-7/adr.Comparison of the gene expresison proflies of two cell lines,a series of genes expressed coincidentally in both gene chip were selected for drug-resistance.There are 1099 genes upregulated in MCF-7/adr and 1275 genes downregulated in MCF-7/adr.They play important role in multiple process including apoptosis,cytoskeleton,signal conduction,cell proliferation/differentiation,regulation of cell cycle,transcription and translation of gene and metabolism of cell.The important genes upregulated are Bcl-2,GSTP1,c-myc,MMP-1 and NNMT;The important genes downregulated are P53,p21Cip1,p27Kip1 and CYPIA1.CONCLUSIONS:These results demonstrate that drug-resistance of breast cancer is very complicated involving many gene upregulated or downregulated expresison.As a new approach,cDNA microarray is feasible to genomewide exploration of gene expression patterns correlated to chemosensitivity.