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Vol. 114, No. 1, 2006
Issue release date: May 2006
Section title: Original Article
Cytogenet Genome Res 114:24–29 (2006)
(DOI:10.1159/000091924)

SLUG (SNAI2) overexpression in embryonic development

Pérez-Mancera P.A. · González-Herrero I. · Maclean K. · Turner A.M. · Yip M.-Y. · Sánchez-Martín M. · García J.L. · Robledo C. · Flores T. · Gutiérrez-Adán A. · Pintado B. · Sánchez-García I.
aLaboratorio 13 and b Laboratorio 12, Instituto de Biología Molecular y Celular del Cáncer (IBMCC), CSIC/Universidad de Salamanca, cServicio de Anatomía Patológica, Universidad de Salamanca, Salamanca; dArea de Reproducción Animal, Centro de Investigación y Tecnología, Madrid (Spain); eDepartment of Medical Genetics, Sydney Children’s Hospital, and fSchool of Women’s and Children’s Health, University of New South Wales; gMolecular & Cytogenetics Unit, Prince of Wales Hospital, Sydney (Australia)

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Article / Publication Details

First-Page Preview
Abstract of Original Article

Published online: 5/24/2006

Number of Print Pages: 6
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: http://www.karger.com/CGR

Abstract

The Snail-related zinc-finger transcription factor, SLUG (SNAI2), is critical for the normal development of neural crest-derived cells and loss-of-function SLUG mutations have been proven to cause piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. However, little is known about the consequences of SLUG overexpression in embryonic development. We report SLUG duplication in a child with a unique de novo 8q11.2→q13.3 duplication associated with tetralogy of Fallot, submucous cleft palate, renal anomalies, hypotonia and developmental delay. To investigate the effects of Slug overexpression on development, we analyzed mice carrying a Slug transgene. These mice were morphologically normal at birth, inferring that Slug overexpression is not sufficient to cause overt morphogenetic defects. In the adult mice, there was a 20% incidence of sudden death, cardiomegaly and cardiac failure associated with incipient mesenchymal tumorigenesis. These findings, while not directly implicating Slug in congenital and acquired heart disease, raise the possibility that Slug overexpression may contribute to specific cardiac phenotypes and cancer development.


Article / Publication Details

First-Page Preview
Abstract of Original Article

Published online: 5/24/2006

Number of Print Pages: 6
Number of Figures: 6
Number of Tables: 0

ISSN: 1424-8581 (Print)
eISSN: 1424-859X (Online)

For additional information: http://www.karger.com/CGR


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Batlle E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A: The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol 2:84–89 (2000).
  2. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al: Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell 114:763–776 (2003).
  3. Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, Portillo F, Nieto MA: The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol 2:76–83 (2000).
  4. Cohen ME, Yin M, Paznekas WA, Schertzer M, Wood S, Jabs EW: Human SLUG gene organization, expression, and chromosome map location on 8q. Genomics 51:468–471 (1998).
  5. du Manoir S, Speicher MR, Joos S, Schrock E, Popp S, Dohner H, et al: Detection of complete and partial chromosome gains and losses by comparative genomic hybridization. Hum Genet 90:590–610 (1993).
  6. Fan YS, Siu VM: Molecular cytogenetic characterization of a derivative chromosome 8 with an inverted duplication of 8p21.3-p23.3 and a rearranged duplication of 8q24.13-qter. Am J Med Genet 102:266–271 (2001).
  7. Garcia-Hernandez B, Castellanos A, Lopez A, Orfao A, Sanchez-Garcia I: Murine hematopoietic reconstitution after tagging and selection of retrovirally transduced bone marrow cells. Proc Natl Acad Sci USA 94:13239–13244 (1997).
  8. Hammond S, Ham R, Stanpfer M: Serum-free growth of human mammary epithelial cells: rapid clonal growth in defined medium and extended passage with pituitary extract. Proc Natl Acad Sci USA 81:5435–5439 (1984).
  9. Inoue A, Seidel MG, Wu W, Kamizono S, Ferrando AA, Bronson RT, et al: Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell 2:279–288 (2002).
  10. Inukai T, Inoue A, Kurosawa H, Goi K, Shinjyo T, Ozawa K, et al: SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol Cell 4:343–352 (1999).
  11. Jiang R, Lan Y, Norton CR, Sundberg JP, Gridley T: The Slug gene is not essential for mesoderm or neural crest development in mice. Dev Biol 198:277–285 (1998).
  12. Nieto MA: The Snail superfamily of zinc finger transcription factors. Nat Rev Mol Cell Biol 3:155–166 (2002).
  13. Nieto MA, Sargent MG, Wilkinson DG, Cooke J: Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264:835–839 (1994).
  14. Oram KF, Carver EA, Gridley T: Slug expression during organogenesis in mice. Anat Rec 271A: 189–191 (2003).
  15. Perez-Losada J, Sanchez-Martin M, Rodriguez-Garcia A, Sanchez ML, Orfao A, Flores T, Sanchez-Garcia I: Zinc-finger transcription factor Slug contributes to the function of the stem cell factor c-kit signaling pathway. Blood 100:1274–1286 (2002).
  16. Perez-Losada J, Sanchez-Martin M, Perez-Caro M, Perez-Mancera PA, Sanchez-Garcia I: The radioresistance biological function of the SCF/kit signaling pathway is mediated by the zinc-finger transcription factor Slug. Oncogene 22:4205–4211 (2003).
  17. Perez-Mancera PA, Gonzalez-Herrero I, Perez-Caro M, Gutierrez-Cianca N, Flores T, Gutierrez-Adan A, et al: SLUG(SNAI2) in cancer development. Oncogene 24:3073–3082 (2005).
  18. Sanchez-Martin M, Rodriguez-Garcia A, Perez-Losada J, Sagrera A, Read AP, Sanchez-Garcia I: SLUG (SNAI2) deletions in patients with Waardenburg disease. Hum Mol Genet 11:3231–3236 (2002).
  19. Sanchez-Martin M, Perez-Losada J, Rodriguez-Garcia A, Gonzalez-Sanchez B, Korf BR, Kuster W, et al: Deletion of the SLUG(SNAI2) gene results in human piebaldism. Am J Med Genet 122A:125–132 (2003).

    External Resources

  20. Sanchez-Martin M, Gonzalez-Herrero I, Sanchez-Garcia I: SNAI2 (SNAIL HOMOLOG 2). Atlas Genet Cytogenet Oncol Haematol, April (2004). (http://www.infobiogen.fr/services/chromcancer/Genes/SNAI2ID453.html).
  21. Savagner P, Yamada KM, Thiery JP: The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J Cell Biol 137:1403–1419 (1997).
  22. Sefton M, Sanchez S, Nieto MA: Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo. Development 125:3111–3121 (1998).
  23. Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, et al: Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet 36:955–957 (2004).