Article

Estrogen and resveratrol regulate Rac and Cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells.

Department of Anatomy and Cell Biology, Universidad Central del Caribe, Bayamon, Puerto Rico.
Neoplasia (New York, N.Y.) (impact factor: 5.48). 03/2007; 9(2):147-58. pp.147-58
Source: PubMed

ABSTRACT Estrogen and structurally related molecules play critical roles in breast cancer. We reported that resveratrol (50 microM), an estrogen-like phytosterol from grapes, acts in an antiestrogenic manner in breast cancer cells to reduce cell migration and to induce a global and sustained extension of actin structures called filopodia. Herein, we report that resveratrol-induced filopodia formation is time-dependent and concentration-dependent. In contrast to resveratrol at 50 microM, resveratrol at 5 microM acts in a manner similar to estrogen by increasing lamellipodia, as well as cell migration and invasion. Because Rho GTPases regulate the extension of actin structures, we investigated a role for Rac and Cdc42 in estrogen and resveratrol signaling. Our results demonstrate that 50 microM resveratrol decreases Rac and Cdc42 activity, whereas estrogen and 5 microM resveratrol increase Rac activity in breast cancer cells. MDA-MB-231 cells expressing dominant-negative Cdc42 or dominant-negative Rac retain filopodia response to 50 microM resveratrol. Lamellipodia response to 5 microM resveratrol, estrogen, or epidermal growth factor is inhibited in cells expressing dominant-negative Rac, indicating that Rac regulates estrogen and resveratrol (5 microM) signaling to the actin cytoskeleton. These results indicate that signaling to the actin cytoskeleton by low and high concentrations of resveratrol may be differentially regulated by Rac and Cdc42.

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Keywords

5 microM acts
 
5 microM resveratrol
 
5 microM resveratrol increase Rac activity
 
50 microM
 
50 microM resveratrol
 
50 microM resveratrol decreases Rac
 
actin cytoskeleton
 
antiestrogenic manner
 
breast cancer
 
breast cancer cells
 
Cdc42 activity
 
cell migration
 
dominant-negative Rac
 
epidermal growth factor
 
estrogen-like phytosterol
 
MDA-MB-231 cells
 
Rac regulates estrogen
 
resveratrol signaling
 
resveratrol-induced filopodia formation
 
Rho GTPases