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Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines.
Giamarchi, C; Solanas, M; Chailleux, C; Augereau, P; Vignon, F; Rochefort, H; Richard-Foy, H.
Afiliación
  • Giamarchi C; Laboratoire de Biologie Moléculaire Eucaryote du CNRS, Toulouse, France.
Oncogene ; 18(2): 533-41, 1999 Jan 14.
Article en En | MEDLINE | ID: mdl-9927210
ABSTRACT
We have compared the DNase I hypersensitivity of the regulatory region of two estrogen-regulated genes, pS2 and cathepsin D in hormone-dependent and -independent breast carcinoma cell lines. This strategy allowed the identification of two important control regions, one in pS2 and the other in cathepsin D genes. In the hormone-dependent MCF7 cell line, within the pS2 gene 5'-flanking region, we detected two major DNase I hypersensitive sites, induced by estrogens and/or IGFI pS2-HS1, located in the proximal promoter and pS2-HS4, located -10.5 Kb from the CAP site, within a region that has not been cloned. The presence of these two DNase I hypersensitive sites correlates with pS2 expression. Interestingly in MCF7 cells, estrogens and IGFI induced indistinguishable chromatin structural changes over the pS2 regulatory region, suggesting that the two transduction-pathways converge to a unique chromatin target. In two cell lines that do not express pS2, MDA MB 231, a hormone-independent cell line that lacks the estrogen receptor alpha, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor alpha, there was only one hormone-independent DNase I hypersensitive site. This site, pS2-HS2, was located immediately upstream of pS2-HS1. In MCF7 cells, two major DNase I hypersensitive sites were present in the 5'-flanking sequences of the cathepsin D gene, which is regulated by estrogens in these cells. These sites, catD-HS2 and catD-HS3, located at positions -2.3 Kb and -3.45 Kb, respectively, were both hormone-independent. A much weaker site, catD-HS1, covered the proximal promoter. In MDA MB 231 cells, that express cathepsin D constitutively, we detected an additional strong hormone-independent DNase I hypersensitive site, catD-HS4, located at position -4.3 Kb. This region might control the constitutive over-expression of cathepsin D in hormone-independent breast cancer cells. All together, these data demonstrate that a local reorganization of the chromatin structure over pS2 and cathepsin D promoters accompanies the establishment of the hormone-independent phenotype of the cells.
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cromatina / Proteínas / Catepsina D / Neoplasias Hormono-Dependientes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 1999 Tipo del documento: Article País de afiliación: Francia
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Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Cromatina / Proteínas / Catepsina D / Neoplasias Hormono-Dependientes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 1999 Tipo del documento: Article País de afiliación: Francia