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.

journal_name

Oncogene

journal_title

Oncogene

authors

Pérez-Mancera PA,González-Herrero I,Pérez-Caro M,Gutiérrez-Cianca N,Flores T,Gutiérrez-Adán A,Pintado B,Sánchez-Martín M,Sánchez-García I

doi

10.1038/sj.onc.1208505

subject

Has Abstract

pub_date

2005-04-28 00:00:00

pages

3073-82

issue

19

eissn

0950-9232

issn

1476-5594

pii

1208505

journal_volume

24

pub_type

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