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.

Key Findings:

Work by these investigators has shown that MCF-7 human breast tumor xenografts require estrogen, acting through the estrogen receptor (ER), to stimulate tumor growth. Once mice are deprived of estrogen, through ovariectomy or administered anti-estrogens, tumors regress.  Soy protein isolate (SPI) and flaxseed (FS), alone and in combination, did not stimulate the growth of established MCF-7 tumors during the first few weeks of estrogen deprivation. After prolonged estrogen deprivation, continuous treatment with SPI induced the growth of MCF-7 tumors, while treatment with FS did not. When FS and SPI were combined, the tumor stimulatory effect of SPI was reduced.  In this study, biomarkers of cell proliferation and IGF-1R signaling were enhanced after 2 weeks in the tumors treated with SPI.  After 25 weeks of treatment, tumor cyclin D1, IGF-1R, Ki-67 LI, ER, and pMAPK continued to be elevated in the SPI tumors.  FS did not show any tumor stimulatory effect on established MCF-7 tumors during both short- and long-term treatment periods. Components of FS including ALA and lignans may be involved in reducing growth factor signaling in tumors.

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, ER, cyclin D1, IGF-IR, and pMAPK and lower ER 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. (Author’s Abstract)