Cancer Res Treat.  2004 Feb;36(1):43-49.

The Differential Gene Expression Profiles between Sensitive and Resistant Breast Cancer Cells to Adriamycin by cDNA Microarray

• Ahn MJ
• Lee KH
• Ahn JI
• Yu DH
• Lee HS
• Choi JH
• Jang JS
• Bae JM
• Lee YS

Abstract

PURPOSE
Adriamycin(R) is one of the most commonly used drugs in the treatment of breast cancer. This study was performed to understand the molecular mechanisms of drug resistance in breast cancer cells. MATERIALS AND METHODS: We have analyzed the MCF-7 breast cell line and its adriamycin-resistant variants, MCF-7/ADR using human 10 K element cDNA microarrays. RESULTS: We defined 68 genes that were up-regulated (14 genes) or down-regulated (54 genes) in adriamycin resistant breast cancer cells. Several genes, such as G protein-coupled receptor kinase 5, phospholipase A2, guanylate cyclase 1, vimentin, matrix metalloproteinase 1 are up-regulated in drug resistant cells. Several genes, such as interferon, alpha-inducible protein 27, forkhead box M1, mitogen-activated protein kinase 6, regulator of mitotic spindle assembly 1 and tumor necrosis factor superfamily are down-regulated in adriamycin resistant cells. The altered expression of genes observed in microarray was verified by RT-PCR. CONCLUSION: These findings show that cDNA microarray analysis can be used to obtain gene expression profiles reflecting the effect of anticancer drugs on breast cancer cells. Such data may lead to the assigning of signature expression profiles of drug-resistant tumors which may help predict responses to drugs and assist in the design of tailored therapeutic regimens to overcome drug resistance.

Keyword

Breast cancer cells; Drug resistance; cDNA microarray; Adriamycin

MeSH Terms

Breast Neoplasms*
Breast*
Cell Line
DNA, Complementary*
Doxorubicin*
Drug Resistance
Gene Expression*
Guanylate Cyclase
Humans
Interferons
Matrix Metalloproteinase 1
Mitogen-Activated Protein Kinase 6
Oligonucleotide Array Sequence Analysis*
Phospholipases A2
Phosphotransferases
Spindle Apparatus
Transcriptome*
Tumor Necrosis Factor-alpha
Vimentin
DNA, Complementary
Doxorubicin
Guanylate Cyclase
Interferons
Matrix Metalloproteinase 1
Mitogen-Activated Protein Kinase 6
Phospholipases A2
Phosphotransferases
Tumor Necrosis Factor-alpha
Vimentin

Figure

• 

  Fig. 1 Verfication of cDNA microarray data by semi-quantitative PCR. A: 1.MCF7 (IFI27), 2.MCF7/ADR (IFI27), 3.MCF7 (TFF1), 4.MCF7/ADR (TFF1), 5.MCF7 (GATA3), 6.MCF7/ADR (GATA3). B: 1.MCF7(GPRK5), 2.MCF7/ADR (GPRK5), 3.MCF7 (GYCY1B3), 4.MCF7/ADR (GYCY1B3), 5.MCF7 (MMP1), 6.MCF7/ADR (MMP1). C: 1. black-MCF7 (IFI27), gray-MCF7/ADR (IFI27), 2.black-MCF7 (TFF1), gray-MCF7/ADR (TFF1), 3. black-MCF7 (GATA3), gray-MCF7/ADR (GATA3) .D: 1.black-MCF7 (GPRK5), gray-MCF7/ADR (GPRK5), 2. black-MCF7 (GYCY1B3), gray-MCF7/ADR(GYCY1B3), 3. black-MCF7 (MMP1), gray-MCF7/ADR (MMP1) IFI27, interferon, alpha-inducible protein 27; TFF, trefoil factor 1; GATA3, GATA-binding protein 3; GPRK5, G protein-coupled receptor kinase 5; GYCY1B3, ×006 protein (MDS006); MMP1, matrix metalloproteinase 1 *OD MCF7-ADR/MCF7 demonstrated relative OD ratio for each MCF7-ADR and MCF7.

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