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SLUG in cancer development.

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 contribute to piebaldism and Waardenburg syndrome type 2 in a dose-dependent fashion. While aberrant induction of SLUG has been documented in cancer cells, relatively little is known about the consequences of SLUG overexpression in malignancy. To investigate the potential role of SLUG overexpression in development and in cancer, we generated mice carrying a tetracycline-repressible Slug transgene. These mice were morphologically normal at birth, and developed mesenchymal tumours (leukaemia and sarcomas) in almost all cases examined. Suppression of the Slug transgene did not rescue the malignant phenotype. Furthermore, the BCR-ABL oncogene, which induces Slug expression in leukaemic cells, did not induce leukaemia in Slug-deficient mice, implicating Slug in BCR-ABL leukaemogenesis in vivo. Overall, the findings indicate that while Slug overexpression is not sufficient to cause overt morphogenetic defects in mice, they demonstrate a specific and critical role for Slug in the pathogenesis of mesenchymal tumours.
AuthorsPedro Antonio Pérez-Mancera, Inés González-Herrero, María Pérez-Caro, Noelia Gutiérrez-Cianca, Teresa Flores, Alfonso Gutiérrez-Adán, Belén Pintado, Manuel Sánchez-Martín, Isidro Sánchez-García
JournalOncogene (Oncogene) Vol. 24 Issue 19 Pg. 3073-82 (Apr 28 2005) ISSN: 0950-9232 [Print] England
PMID15735690 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Complementary
  • SNAI1 protein, human
  • SNAI2 protein, human
  • Snai2 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors
  • Fusion Proteins, bcr-abl
Topics
  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • DNA, Complementary (metabolism)
  • Female
  • Fusion Proteins, bcr-abl (metabolism)
  • Heterozygote
  • Homozygote
  • Humans
  • K562 Cells
  • Leukemia (etiology, genetics)
  • Male
  • Mesoderm (metabolism)
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Models, Biological
  • Models, Genetic
  • Mutation
  • Neoplasm Transplantation
  • Neoplasms (etiology, metabolism)
  • Neoplasms, Experimental (metabolism)
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Time Factors
  • Transcription Factors (genetics, physiology)
  • Transfection
  • Transgenes
  • U937 Cells

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