Changes in biomarkers of estrogen receptor and growth factor signaling pathways in MCF-7 tumors after short- and long-term treatment with soy and flaxseed

Abstract

Previously we have shown that MCF-7 human breast tumor growth is stimulated after prolonged treatment with dietary soy protein isolate (SPI). However, the effects are attenuated when SPI is combined with flaxseed (FS). This study determined the changes that occur in tumor growth biomarkers, after both short- and long-term treatment with SPI, FS or their combination, to help identify signaling pathways potentially involved in SPI-stimulated tumor growth. Ovariectomized mice with established MCF-7 tumors were fed basal diet (control), 20%SPI, 10%FS, or SPI + FS for 2 or 25 weeks. After 2 weeks, there were no differences in tumor size, however, compared with control, SPI-treated tumors had higher IGF-IR and cyclin D1 while FS and SPI + FS-fed mice had lower pMAPK expression. After 25 weeks, SPI-treated tumors were larger, had higher proliferation, ERα, cyclin D1, IGF-IR, and pMAPK and lower ERβ and HER2 levels. When combined with FS, however, the effects on these tumor biomarkers induced by SPI were attenuated. This study demonstrates that SPI and FS differently modulate tumor biomarkers of estrogen and growth factor signaling pathways, after both short- and long-term treatment, which may indicate a role of these pathways in the tumor stimulatory effects of SPI and the tumor inhibitory effects of FS.