Actions of Tamoxifen and Estrogen on Osteoblast Protein Kinase C expression.

摘要

Tamoxifen is a major therapeutic agent in the treatment of breast cancer. While tamoxifen acts as an estrogen antagonist in breast tissue, its actions on other tissues reflect a range of estrogenic and antiestrogenic activity. Both estrogen and tamoxifen act to preserve bone mass, but the mechanisms underlying this effect are not fully understood. The goal of this study was to determine the effects of estrogen and tamoxifen on protein kinase C (PKC) isozyme expression in osteoblasts; this signaling pathway is estrogen- responsive in other tissues. We have established the PKC isozyme profile in a number of normal and tumor-derived osteoblast cell lines. The characteristic isozymes present in these cells are PKC-a, B, E, l and t. The time course and dose dependence of their regulation by the phorbol ester phorbol 12, 13- dibutyrate was also defined. A number of different treatment protocols for estrogen and tamoxifen were employed. Both 72 h and 7 day treatment of subconfluent UMR-1O6 cells with tamoxifen increased the expression of PKC-P1; additional experiments are necessary to further characterize these effects. Future directions of this research will explore the role of this isozyme in the actions of tamoxifen on bone.