The objective of this proposal is to delineate novel signaling mechanisms of resveratrol that may directly inhibit breast cancer progression to the metastatic state. The hypothesis is that resveratrol inhibits breast cancer cell migration by modulating the actin cytoskeleton via a rapid signaling cascade that does not involve classic estrogen receptor (ER)-mediated effects on gene transcription.
The specific aims are: to determine if the effect of resveratrol on the actin cytoskeleton of breast cancer cells is ER- and/or epidermal growth factor receptor (EGFR)-dependent, to identify the signaling intermediates that regulate resveratrol-induced changes in the actin cytoskeleton, and to delineate potential direct mechanisms of resveratrol-induced signaling to the actin cytoskeleton. An array of breast cancer cell lines will be analyzed. ER and EGFR dependence will be determined by inhibitor studies and analyzed by cell biological and biochemical assays. Signaling intermediates will be identified by molecular biology techniques involving creation and expression analysis of mutants of proteins implicated in resveratrol signaling by our preliminary data. This research will contribute to understanding the therapeutic and cancer preventive capabilities of this dietary component. ? ?
| Azios, Nicolas G; Krishnamoorthy, Lakshmi; Harris, Micheleen et al. (2007) Estrogen and resveratrol regulate Rac and Cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells. Neoplasia 9:147-58 |
