Abstract 1988: Increased expression of eukaryotic protein synthesis initiation factor eIF4G by the daidzein metabolite equol may contribute to breast cancer malignancy

Abstract

Abstract The role of dietary soy in cancer has been the subject of intense investigation and is thought to be cancer preventive. However, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein and combined soy isoflavones (genistein, daidzein, and glycitein) promoted breast cancer progression in a nude mouse model by increasing both primary mammary tumor growth and metastasis. Dietary daidzein significantly upregulated cancer promoting molecules including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E. Herein, using tumors from mice treated orally with daidzein, we show that increased eIF expression is associated with expression of mRNAs with long structured 5′ untranslated regions and internal ribosomal entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. We then tested the hypothesis that daidzein upregulates protein synthesis initiation in breast cancer, but found that daidzein treatment did not affect the levels of eIFs in the same MDA-MB-435 cell line in vitro. Therefore, we tested the effect of equol that is metabolized from daidzein by the gut bacteria in mice and humans. Results show that equol specifically upregulated eIF4G, but not eIF4E, in MDA-MB-435 and MDA-MB-231 human breast cancer cells. Equol treatment also increased gene and protein expression of c-MYC and protein expression of other cell survival and proliferation promoting molecules with IRES sites. The elevated eIF4G in response to equol was not associated with eIF4E in a cap binding co-capture assay. Therefore, upregulation of eIF4G by equol may regulate cap-independent protein synthesis initiation resulting in cancer cell survival, proliferation, and thus, tumor progression. This research was supported by grant numbers US Army/BCRP W81XWH-11-1-0199 to CD, to NIH/NIGMS SC3GM084824 to SD Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1988. doi:1538-7445.AM2012-1988