ARTICLES Association Between Pak1 Expression and Subcellular Localization and Tamoxifen Resistance in Breast Cancer Patients

many proteins in both normal and transformed cells. Its abil-ity to phosphorylate and thereby activate the estrogen recep-tor α (ER α) potentially limits the effectiveness of antiestrogen treatment in breast cancer. Here we studied associations between Pak1 expression and subcellular localization in tumor cells and tamoxifen resistance. Methods: Pak1 protein expression was evaluated in 403 primary breast tumors from premenopausal patients who had been randomly assigned to 2 years of adjuvant tamoxifen or no treatment. Tamoxifen response was evaluated by comparing recurrence-free sur-vival in relation to Pak1 and ER α expression in untreated versus tamoxifen-treated patients. Tamoxifen responsiveness of human MCF-7 breast cancer cells that inducibly expressed constitutively active Pak1 or that transiently overexpressed wild-type Pak1 (Wt-Pak1) or Pak1 that lacked functiona