Abstract
Physiological concentration of genistein, a natural isoflavonoid phytoestrogen, stimulates human breast cancer (MCF-7) cells proliferation. In this study, we hypothesize that low concentration of genistein mimics the action of 17beta-estradiol in stimulation of MCF-7 cell growth by enhancement of IGF-I signaling pathway. Genistein, at 1 microM, stimulated the growth of MCF-7 cells. Cell cycle analysis showed that 1 micro M genistein significantly increased the S phase and decreased the G0G1 phase of MCF-7 cells. The protein and mRNA expression of IGF-I receptor (IGF-IR) and insulin receptor substrate (IRS)-1, but not Src homology/collagen protein, increased in response to 1 microM genistein in a time-dependent manner. These effects could be completely abolished by cotreatment of MCF-7 cells with estrogen antagonist ICI 182780 (1 microM) and tamoxifen (0.1 microM). Our results also showed that genistein induction of IGF-IR and IRS-1 expression resulted in enhanced tyrosine phosphorylation of IGF-IR and IRS-1 on IGF-I stimulation. Taken together, these data provide the first evidence that the IGF-IR pathway is involved in the proliferative effect of low-dose genistein in MCF-7 cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adaptor Proteins, Vesicular Transport / metabolism
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Cycle / drug effects
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Cell Division / drug effects
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Cell Line, Tumor
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Dose-Response Relationship, Drug
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Estradiol / pharmacology
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Estrogen Receptor alpha
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Genistein / administration & dosage
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Genistein / pharmacology*
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Humans
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Insulin Receptor Substrate Proteins
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Kinetics
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Osmolar Concentration
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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RNA, Messenger / metabolism
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Receptor, IGF Type 1 / genetics
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Receptor, IGF Type 1 / metabolism
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Receptors, Estrogen / antagonists & inhibitors
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Receptors, Estrogen / genetics
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Shc Signaling Adaptor Proteins
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Signal Transduction / drug effects*
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Somatomedins / metabolism*
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Src Homology 2 Domain-Containing, Transforming Protein 1
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Estrogen Receptor alpha
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IRS1 protein, human
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Insulin Receptor Substrate Proteins
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Phosphoproteins
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RNA, Messenger
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Receptors, Estrogen
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SHC1 protein, human
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Shc Signaling Adaptor Proteins
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Somatomedins
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Src Homology 2 Domain-Containing, Transforming Protein 1
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Estradiol
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Genistein
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Receptor, IGF Type 1