Concentration-dependent effects of genistein on global gene expression in MCF-7 breast cancer cells: an oligo microarray study.
Breast cancer is the most commonly diagnosed cancer among US women; there is therefore great interest in developing preventive and treatment strategies for this disease. Because breast cancer incidence is much lower in countries where women consume high levels of soy, bioactive compounds in this food source have been studied for their effects on breast cancer. Genistein, found at high levels in soybeans and soy foods, is a controversial candidate breast cancer preventive phytochemical whose effects on breast cells are complex. To understand more clearly the molecular mechanisms underlying the effects of genistein on breast cancer cells, we used a DNA oligo microarray approach to examine the global gene expression patterns in MCF-7 breast cancer cells at both physiologic (1 or 5 microM) and pharmacologic (25 microM) genistein concentrations. Microarray analyses were performed on MCF-7 cells after 48 h of either vehicle or 1, 5, or 25 microM genistein treatment. We found that genistein altered the expression of genes belonging to a wide range of pathways, including estrogen- and p53-mediated pathways. At 1 and 5 microM, genistein elicited an expression pattern suggestive of increased mitogenic activity, confirming the proliferative response to genistein observed in cultured MCF-7 cells, while at 25 microM genistein effected a pattern that likely contributes to increased apoptosis, decreased proliferation and decreased total cell number, also consistent with cell culture results. These findings provide evidence for a molecular signature of genistein's effects in MCF-7 cells and lay the foundation for elucidating the mechanisms of genistein's biological impact in breast cancer cells.
Lavigne
Jackie A
JA
Division of Cancer Prevention, National Cancer Institute, NIH, Bethesda, MD, USA.
Takahashi
Yoko
Y
Chandramouli
Gadisetti V R
GV
Liu
Huaitian
H
Perkins
Susan N
SN
Hursting
Stephen D
SD
Wang
Thomas T Y
TT
D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D051025:bcl-Associated Death Protein / Q000235:genetics; D000097642:GADD45 Proteins
D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004958:Estradiol; D019833:Genistein; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D016159:Tumor Suppressor Protein p53; D051025:bcl-Associated Death Protein; C494819:BAD protein, human; C096820:BIK protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C105190:TNFRSF10A protein, human