Estrogen and the Dietary Phytoestrogen Resveratrol as Regulators of the Rho GTPase Rac in Breast Cancer Metastasis
Final rept. 1 Jun 2007-22 Aug 2011
PUERTO RICO UNIV SAN JUAN
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The hypothesis that estrogen and low concentrations of resveratrol promote breast cancer invasion and metastasis while high concentrations of resveratrol prevent breast cancer metastasis via regulation of Rac was tested. Results from Specific Aim 1 demonstrated that dependent on estrogen receptor ER status, E2 and resveratrol have differential effects on Rac activity, cell migrationinvasion, and cell growth. Specific Aim 2, we tested the effect of resveratrol on mammary tumor growth and metastasis. At all concentrations tested, resveratrol increased mammary tumor growth and lung metastasis and enhanced Rac activity. Since the Rac activity of breast cancer cells could not be inhibited by a commercially available Rac inhibitor NSC-23766, we developed novel Rac inhibitors as anti breast cancer metastasis compounds Hernandez, et al., 2010, Montalvo et al., in review. Resveratrol in combination with other grape polyphenols reduced breast cancer growth and metastasis to bone and liver by inhibition of PI3-K signaling Castillo et al., 2009 Castillo et al., in review.
- Anatomy and Physiology
- Medicine and Medical Research