ESTROGEN REGULATES THE ASSOCIATION OF INTERMEDIATE FILAMENT PROTEINS WITH NUCLEAR-DNA IN HUMAN BREAST-CANCER CELLS

In a previous study we showed that the levels of the intermediate fila ment proteins, cytokeratins 8, 18, and 19, in the nuclear matrix-inter mediate filament (NM-IF) fraction from the hormone-dependent and estro gen receptor (ER)-positive human breast cancer cell line T-47D5 were r egulated by estrogens. In contrast, estrogens did not regulate the cyt okeratins in the NM-IF fraction of the hormone-independent and ER-posi tive cell line, T5-PRF. In this study, human breast cancer cells were treated with cis-diamminedichloroplatinum to cross-link protein to nuc lear DNA in situ, and proteins bound to DNA were isolated. We show tha t cytokeratins 8, 18, and 19 of T-47D5 and T5-PRF were associated with nuclear DNA in situ. The levels of the cytokeratins 8, 18, and 19 bou nd to nuclear DNA or associated with the cytoskeleton of T-47D5 human breast cancer cells decreased when estrogens were depleted or the pure antiestrogen ICI 164,384 was added. In contrast, the cytokeratin leve ls associated with nuclear DNA or cytoskeleton were not significantly affected by estrogen withdrawal or antiestrogen administration in TB-P RF cells. These observations suggest that estrogen regulates the organ ization of nuclear DNA by rearrangement of the cytokeratin filament ne twork in hormone-dependent, ER-positive human breast cancer cells and that this regulation is lost in hormone-independent, ER-positive breas t cancer cells.