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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

Oncogene volume 18, pages 533–541 (1999)Cite this article

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 α, and HE5, a cell line derived from MDA MB 231 by transfection that expresses estrogen receptor α, 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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References

  • Augereau P, Miralles F, Cavailles V, Gaudelet C, Parker M and Rochefort H. . 1994 Mol. Endocrinol. 8: 693–703.

  • Bannister J and Kouzarides T. . 1996 Nature 384: 641–643.

  • Berry M, Nunez AM and Chambon P. . 1989 Proc. Natl. Acad. Sci. USA 86: 1218–1222.

  • Brzozowski AM, Pike AC, Dauter Z, Hubbard RE, Bonn T, Engstrom O, Ohman L, Greene GL, Gustafsson JA and Carlquist M. . 1997 Nature 389: 753–758.

  • Cailleau R, Young R, Olive M and Reeves Jr WJ. . 1974 J. Natl. Cancer Inst. 53: 661–674.

  • Carr KD and Richard-Foy H. . 1990 Proc. Natl. Acad. Sci. USA 87: 9300–9304.

  • Cavailles V, Augereau P and Rochefort H. . 1993 Proc. Natl. Acad. Sci. USA 90: 203–207.

  • Cavailles V, Garcia M and Rochefort H. . 1989 Mol. Endocrinol. 3: 552–558.

  • Chalbos D, Joyeux C, Galtier F and Rochefort H. . 1992 J. Steroid Biochem. Mol. Biol. 43: 223–228.

  • Chalbos D, Philips A, Galtier F and Rochefort H. . 1993 Endocrinology 133: 571–576.

  • Dumont JA, Bitonti AJ, Wallace CD, Baumann RJ, Cashman EA and Cross-Doersen DE. . 1996 Cell Growth Differ. 7: 351–359.

  • Foekens JA, van Putten WL, Portengen H, de Koning HY, Thirion B, Alexieva-Figusch J and Klijn JG. . 1993 J. Clin. Oncol. 11: 899–908.

  • Garcia M, Derocq D, Freiss G and Rochefort H. . 1992 Proc. Natl. Acad. Sci. USA 89: 11538–11542.

  • Gillesby BE, Stanostefano M, Porter W, Safe S, Wu ZF and Zacharewski TR. . 1997 Biochemistry 36: 6080–6089.

  • Kato S, Endoh H, Masuhiro Y, Kitamoto T, Uchiyama S, Sasaki H, Masushige S, Gotoh Y, Nishida E, Kawashima H, Metzger D and Chambon P. . 1995 Science 270: 1491–1494.

  • Krishnan V, Wang X and Safe S. . 1994 J. Biol. Chem. 269: 15912–15917.

  • Levenson AS and Jordan VC. . 1994 J. Steroid Biochem. Mol. Biol. 51: 229–239.

  • Martin V, Ribieras S, Song-Wang XG, Lasne Y, Frappart L, Rio MC and Dante R. . 1997 J. Cell. Biochem. 65: 95–106.

  • Montminy M. . 1997 Nature 387: 654–655.

  • Nakajima T, Uchida C, Anderson SF, Lee CG, Hurwitz J, Parvin JD and Montminy M. . 1997 Cell 90: 1107–1112.

  • Nunez AM, Berry M, Imler JL and Chambon P. . 1989 EMBO J. 8: 823–829.

  • Reese JC and Katzenellenbogen BS. . 1992 Mol. Cell. Biol. 12: 4531–4538.

  • Richard-Foy H and Hager GL. . 1987 EMBO J. 6: 2321–2328.

  • Richard-Foy H, Sistare FD, Riegel AT, Simons Jr SS and Hager GL. . 1987 Mol. Endocrinol. 1: 659–665.

  • Rochefort H. . 1990 Breast Cancer Res. Treat. 16: 3–13.

  • Sewack GF and Hansen U. . 1997 J. Biol. Chem. 272: 31118–31129.

  • Soule HD, Vazguez J, Long A, Albert S and Brennan M. . 1973 J. Natl. Cancer Inst. 51: 1409–1416.

  • Tora L, Mullick A, Metzger D, Ponglikitmongkol M, Park I and Chambon P. . 1989 EMBO J. 8: 1981–1986.

  • Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK and Rosenfeld MG. . 1997 Nature 387: 677–684.

  • Touitou I, Vignon F, Cavailles V and Rochefort H. . 1991 J. Steroid Biochem. Mol. Biol. 40: 231–237.

  • Vignon F, Bouton MM and Rochefort H. . 1987 Biochem. Biophys. Res. Commun. 146: 1502–1508.

  • Vladusic EA, Hornby AE, Guerra-Vladusic FK and Lupu R. . 1998 Cancer Res. 58: 210–214.

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Acknowledgements

We thank MC Rio and P Chambon for pS2 probes. We are grateful to JC Faye for stimulating discussions and to Y Henry for critically reading the manuscript. CG was the recipient of fellowships from Association pour la Recherche sur le Cancer and Fondation pour la Recherche Médicale and MS was supported by a fellowship from Comissionat per a Universitats i Recerca. Generalitat de Catalunya. This work was partially supported by the Association pour la Recherche sur le Cancer, the Ligue Contre le Cancer, the Conseil de Region Midi Pyrénées and the European Economic Community, Biomed 2 contract PL95-0181.

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Authors and Affiliations

  1. Laboratoire de Biologie Moléculaire Eucaryote du CNRS, 118 route de Narbonne, Toulouse, 31062, cedex-, France

    Claire Giamarchi, Catherine Chailleux & Hélène Richard-Foy

  2. Departament de Biologia Cel.lular i Fisiologia, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain

    Monserrat Solanas

  3. Unité Hormones et Cancer, U-148 INSERM, 60 rue de Navacelles, 34090, Montpellier, France

    Patrick Augereau, Francoise Vignon & Henri Rochefort

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  1. Claire Giamarchi
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Giamarchi, C., Solanas, M., Chailleux, C. et al. Chromatin structure of the regulatory regions of pS2 and cathepsin D genes in hormone-dependent and -independent breast cancer cell lines. Oncogene 18, 533–541 (1999). https://doi.org/10.1038/sj.onc.1202317

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