ESTROGEN REGULATION OF NUCLEAR MATRIX-INTERMEDIATE FILAMENT PROTEINS IN HUMAN BREAST-CANCER CELLS

The tissue matrix consists of linkages and interactions of the nuclear matrix, cytoskeleton, and extracellular matrix. This system is a dyna mic structural component of the cell that organizes and processes stru ctural and functional information to maintain and coordinate cell func tion and gene expression. We have studied estrogen regulation of nucle ar matrix associated proteins, including the intimately connected cyto skeletal intermediate filaments, in T-47D5 human breast cancer cells. Three proteins (identified as cytokeratins 8, 18, and 19) present in t he nuclear matrix-intermediate filament fraction (NM-IF) of cells grow n in estrogen-replete conditions were dramatically reduced when the ce lls were grown in acute (1 week) estrogen-depleted conditions. Replaci ng estrogen in the medium of acute estrogen-depleted cells restored ex pression of these proteins. T-47D5 cells that are chronically depleted of estrogen (T5-PRF) are estrogen-nonresponsive in culture. These cel ls overexpressed these three proteins, compared to parent cells grown in the presence of estrogen. Treatment of the T5-PRF cells with estrog en did not lead to further up-regulation of these proteins. Treating T -47D5 cells in estrogen-replete conditions with the antiestrogens 4-hy droxytamoxifen and ICI 164 384 (100 nM, 3 days) resulted in a signific ant reduction in these proteins, while no effect was seen in long-term chronic estrogen-depleted T-47D5 cells. In conclusion, we have identi fied NM-IF proteins (cytokeratins 8, 18, and 19) in human breast cance r cells that are estrogen regulated and may play a role in estrogen ac tion in human breast cancer cells. (C) 1996 Wiley-Liss, Inc.