Abstract
In a previous study we showed that the levels of the intermediate filament proteins, cytokeratins 8, 18, and 19, in the nuclear matrix-intermediate filament (NM-IF) fraction from the hormone-dependent and estrogen receptor (ER)-positive human breast cancer cell line T-47D5 were regulated by estrogens. In contrast, estrogens did not regulate the cytokeratins in the NM-IF fraction of the hormone-independent and ER-positive cell line, T5-PRF. In this study, human breast cancer cells were treated with cis-diamminedichloroplatinum to cross-link protein to nuclear DNA in situ, and proteins bound to DNA were isolated. We show that 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 bound 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 levels associated with nuclear DNA or cytoskeleton were not significantly affected by estrogen withdrawal or antiestrogen administration in T5-PRF cells. These observations suggest that estrogen regulates the organization of nuclear DNA by rearrangement of the cytokeratin filament network in hormone-dependent, ER-positive human breast cancer cells and that this regulation is lost in hormone-independent, ER-positive breast cancer cells.
Highlights
The nuclear matrix (NM),1 cytoskeleton (CSK), and extracellular matrix form the tissue matrix system, a mechanically continuous skeletal network thought to govern nuclear shape and function [1,2,3]
Levels of cis-DDP DNA-Cross-linked Cytokeratins 8, 18, and 19 Are Influenced by Estrogen and Antiestrogen in a Hormonedependent Human Breast Cancer Cell Line—Our previous study showed that the levels of cytokeratins in the nuclear matrix-intermediate filament (NM-IF) fraction of T-47D5 cells were regulated by estradiol [18]
T-47D5 cells grown in the absence or presence of estradiol were incubated with cis-DDP, and the proteins cross-linked to DNA were isolated
Summary
The nuclear matrix (NM),1 cytoskeleton (CSK), and extracellular matrix form the tissue matrix system, a mechanically continuous skeletal network thought to govern nuclear shape and function [1,2,3]. In an analysis of the NM-IF (nuclear matrix with associated intermediate filaments) fraction of T-47D5 human breast cancer cells (ER-positive and hormone-dependent), we identified the principal NM-IF proteins as cytokeratins 8, 18, and 19 [18]. In a hormone-independent, ER-positive human breast cancer cell line (T5-PRF), cytokeratins in the NM-IF were maintained at high levels regardless of whether the cells were grown in the presence or absence of estrogens [18].
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