SLUG in cancer development.
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.
Pérez-Mancera
Pedro Antonio
PA
Laboratorio 13, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Campus Unamuno, 37007-Salamanca, Spain.
González-Herrero
Inés
I
Pérez-Caro
María
M
Gutiérrez-Cianca
Noelia
N
Flores
Teresa
T
Gutiérrez-Adán
Alfonso
A
Pintado
Belén
B
Sánchez-Martín
Manuel
M
Sánchez-García
Isidro
I
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000209:etiology / Q000235:genetics; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000209:etiology / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000378:metabolism; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014162:Transfection; D019076:Transgenes; D020298:U937 Cells
D018076:DNA, Complementary; C000604407:SNAI1 protein, human; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl