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Pak1 Expression and Tamoxifen Resistance

Phosphorylation and activation of estrogen receptor α (ERα) by p21-activated kinase 1 (Pak1) could limit the effectiveness of antiestrogen treatment in breast cancer. Holm et al. (p. 671 ) evaluated Pak1 protein expression and subcellular localization in primary breast tumors from premenopausal patients who had been randomly assigned to receive 2 years of adjuvant tamoxifen or no treatment and compared tamoxifen response in relation to Pak1 and ERα expression. Among patients with ERα–positive tumors with low Pak1 expression, those treated with tamoxifen had better recurrence-free survival than those who received no treatment; for patients whose tumors had high cytoplasmic or any nuclear Pak1 expression, recurrence-free survival did not differ between treatment groups. Overexpression of wild-type Pak1, but not of Pak1 lacking functional nuclear localization signals, in human MCF-7 breast cancer cells compromised tamoxifen response. The authors conclude that Pak1, particularly nuclear Pak1, may have a role in ERα signaling and in tamoxifen resistance.