Tamoxifen Dependent Interaction Between in Estrogen Receptor and a Novel p21 Activated Kinase

摘要

The classical estrogen receptor, estrogen receptor alpha (ERalpha) plays an important role in breast cancer development and a large fraction of ERalpha positive breast cancers respond to treatment with tamoxifen. We cloned a novel p2l activated kinase (PAK), termed PAK6, which binds to the androgen receptor (AR) and selectively to the 4-hydroxytamoxifen (OHT) liganded ERalpha. PAKs are a family of serine/threonine kinases that bind to and are regulated by the active (GTP bound) form of the Rho family small (p2l) GTPases, Cdc42 and Rac. We found that PAK6 transcripts were expressed in normal mammary epithelium and our preliminary data showed a possible alternative splice product in breast cancer cell lines, indicating that PAK6 may play a role in breast cancer. The purpose of this research was to assess PAK6 expression in breast cancer and to determine whether it contributes to ERalpha function in breast cancer cells or to tamoxifen responses.