Alterations of Metastasis-Related Genes Identified Using an Oligonucleotide Microarray of Genistein-Treated HCC1395 Breast Cancer Cells

Abstract

Genistein, one of the major isoflavones, potently inhibits the growth and metastasis of breast cancer. However, the precise molecular mechanism in metastasis inhibition is not clear. We investigated the effect of genistein in HCC1395 cells, a cell line derived from an early-stage primary breast cancer. Genistein dose dependently both decreased cell viability and inhibited the invasion potential. We used human oligonucleotide microarrays to determine the gene expression profile altered by genistein treatment. TFPI-2, ATF3, DNMT1, and MTCBP-1, which inhibit invasion and metastasis, were upregulated, and MMP-2, MMP-7, and CXCL12, which promote invasion and metastasis, were downregulated. We used quantitative real-time polymerase chain reaction to verify the microarray data at the mRNA level. We conclude that genistein-induced alternations of gene expression involving metastasis may be exploited for devising chemopreventive and therapeutic strategies, particularly for early-stage breast cancer.

Acknowledgments and Notes

This work is supported by grants from the National Science Council (92-2320-B-006-072, NSC 93-2320-B-384-003, 94-2320-B-384-001) and Chi Mei Medical Center (CMNSC-9304, CMNSC-9403), Taiwan.

Notes

^a Abbreviations are as follows: RT-PCR, reverse transcription polymerase chain reaction; MMP, matrix metalloproteinase; CXCL12, chemokine (C-X-C motif) ligand 12; TPFI-2, tissue factor pathway inhibitor-2; ATF3, activating transcription factor 3; DNMT1, DNA methyltransferase 1; MTCBP-1, membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1.

^a The values are the mean ± standard error of the mean of 3 independent experiments.∗, P < 0.001 vs. control; †, P < 0.01 vs. control. Sub-G1, apoptotic peak; G0/G1, border quiescent to gap 1 phase; S, DNA synthesis phase; G2/M, border gap 2 to mitosis phase.

^a Abbreviation is as follows: qRT-PCR, quantitative real-time reverse transcription polymerase chain reaction. ∗Fold changes are shown as log₂ values.