Chromatin remodeling in hormone-dependent and independent human breast cancer cell lines

Chromatin restricts the accessibility of DNA to regulatory factors, its rem odeling over the regulatory regions contributes to the control of gene expr ession. An increasing number of evidence links defects in chromatin remodel ing machinery and cancer. Our aim is to elucidate the role of chromatin str ucture in the control of the expression of hormone-induced genes in breast cell lines estrogen-dependent or -independent for growth. Mammary tumor gro wth is controlled by steroid hormones via their nuclear receptor and by gro wth factors via tyrosine kinase receptors. 50 % of these tumors elude to ho rmonal control. This limits the anti-estrogen therapy. As a model, we have analyzed in several cell lines the chromatin organization of the regulatory regions of two genes, pS2 that is associated with a good prognostic, and c athepsin D (catD) that is a bad prognostic marker. The expression of the tw o genes is estrogen-regulated in estrogen-dependent cell line MCF7. In cont rast in the hormone-independent cell line MDA MB 231, pS2 is not expressed and catD is constitutively expressed. Within the regulatory regions of pS2 gene, we have localized two regions that undergo a hormone-dependent change in chromatin structure in MCF7 cells but not in MDA MB 231. The lack of ch romatin remodeling in MDA MB 231 cells is not due to the absence of express ion of the estrogen receptor in the cell line. The expression of pS2 gene c an be correlated with chromatin remodeling over the regulatory regions of p S2 gene, In contrast catD regulatory regions did not display hormone-depend ent changes in chromatin structure, suggesting that hormone regulation take s place within regions with a constitutively open chromatin structure.