Objective      To investigate the rearrangement of filament actin（F-actin） cytoskeleton during the development of tamoxifen resistance in human breast cancer MCF-7 cells.       Methods      MCF-7 tamoxifen-resistant (Tam-R) cells were derived from wild-type MCF-7 (MCF-7W) cells by exposure to a high concentration of 4-hydroxytamoxifen (OHT) for a short period. The dynamic change of F-actin was

visualized by FITC-Phalloidin staining. Immunofluorescence staining was used to evaluate the expression and distribution of E-cadherin in MCF-7W and Tam-R cells. Pull-down assay and Western blot analysis were utilized to analyze the activity of small GTPases Rac1. Transwell assay was used to evaluate the effects of F-actin cytoskeleton rearrangement on migratory ability of Tam-R cells.       Results      In MCF-7W cells

F-actin concentrated along the cell membrane like pebbles

and E-cadherin

distributed like F-actin

formed strong intercellular adhesion junction. In contrast

abnormal lamellipodia

stress fiber and reduced E-cadherin-mediated cell-cell adhesion were observed in Tam-R cells. Additionally

the PI3K inhibitor Wortmannin (WM) attenuated the activity of Rac1

rearrangement of actin cytoskeleton and cell migration（

P

0.05） induced by tamoxifen in Tam-R cells. The inhibitor of ERK

U0126

had few effects on the actin cytoskeleton rearrangement induced by OHT.       Conclusion      OHT probably activates PI3K and promotes Rac1 activation

and to promote the migration in Tam-R cells by inducing the rearrangement of actin cytoskeleton.