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Table 1 Summary of the ERα-dependent and independent activities of genistein and isoflavones on signal transduction pathways

From: Does consuming isoflavones reduce or increase breast cancer risk?

Compound Effect Test system* ERα dependence References
Genistein Inhibition of tyrosine-specific protein kinase activity of EGFR, pp60v-src and pp110gag-fes In vitro assay and A431 cells Not assessed [24]
Genistein Inhibition of the MEK5/ERK5/NF-κB pathway, leading to apoptosis MDA-MB-231 cells ERα-independent [25]
Genistein G2/M-phase cell cycle arrest through activation of phosphorylated ERK1/2 MDA-MB-231 cells ERα-independent [26]
Genistein Downregulation of the PI 3-kinase/Akt signaling pathway, leading to inhibition of estrogen-induced proliferation MCF7 cells ERα-dependent [27]
Genistein Repression of HER2 protein expression, phosphorylation and HER2 promoter activity BT-474 cells transfected with either ERα or ERβ Both ERα-dependent and independent effects [28]
Genistein Inhibition of proliferation and induction of apoptosis in BRCA1 mutant cells through p21CIP/WAF and Akt. Cells with wild-type BRCA1 were more resistant to effects of genistein MDA-MB-231 cells (wild-type BRCA1); HCC1937, SUM149 and SUM1315 cells (mutated BRCA1) Not assessed [29]
Genistein Activation of cell growth through increased IGF-1 receptor gene expression MCF-7 cells Both ERα-dependent and independent effects [30]
Isoflavones AR, PR and PPARγ binding and activation In vitro ligand binding assay, yeast transcription activation assay ERα-independent [31]
  1. *Cell lines: MCF-7, an ERα-positive breast tumor line; MDA-MB-231, an ERα-negative breast tumor line; MCF-10a, an ERα-negative fibrocystic breast cell line; HCC1937, SUM149 and SUM1315, breast cancer cell lines with mutated BRCA1; BT-474, a breast cancer line; A431, an epidermoid carcinoma line. Other abbreviations: AR, androgen receptor; BRCA1, breast cancer 1; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; HER2, human epidermal growth factor receptor 2; IGF-1, insulin-like growth factor 1; MEK, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; p21CIP/WAF, cyclin kinase inhibitor p21; PI, phosphatidylinositol; PPARγ, peroxisome proliferator-activated receptor gamma; PR, progesterone receptor; pp60v-src, protein kinase encoded by the transforming gene (v-src) of Rous sarcoma virus; pp110gag-fes, tyrosine kinase encoded by the transforming gene (v-fes) of Feline sarcoma virus.