Disabled-2 downregulation promotes epithelial-to-mesenchymal transition

J. C. Martin, Brittney-Shea Herbert, B. A. Hocevar

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Metastatic tumour cells are characterised by acquisition of migratory and invasive properties; properties shared by cells, which have undergone epithelial-to-mesenchymal transition (EMT). Disabled-2 (Dab2) is a putative tumour suppressor whose expression has been shown to be downregulated in various cancer types including breast cancer; however, its exact function in suppressing tumour initiation or progression is unclear. Methods: Disabled-2 isoform expression was determined by RT-PCR analysis in human normal and breast tumour samples. Using shRNA-mediated technology, Dab2 was stably downregulated in two cell model systems representing nontumourigenic human mammary epithelial cells. These cells were characterised for expression of EMT markers by RT-PCR and western blot analysis. Results : Decreased expression of the p96 and p67 isoforms of Dab2 is observed in human breast tumour samples in comparison to normal human breast tissue. Decreased Dab2 expression in normal mammary epithelial cells leads to the appearance of a constitutive EMT phenotype. Disabled-2 downregulation leads to increased Ras/MAPK signalling, which facilitates the establishment of an autocrine transforming growth factor Β (TGFΒ) signalling loop, concomitant with increased expression of the TGFΒ2 isoform. Conclusion : Loss of Dab2 expression, commonly observed in breast cancer, may facilitate TGFΒ-stimulated EMT, and therefore increase the propensity for metastasis.

Original languageEnglish
Pages (from-to)1716-1723
Number of pages8
JournalBritish Journal of Cancer
Volume103
Issue number11
DOIs
StatePublished - Nov 23 2010

Fingerprint

Epithelial-Mesenchymal Transition
Down-Regulation
Breast Neoplasms
Protein Isoforms
Breast
Transforming Growth Factors
Epithelial Cells
Neoplasms
Polymerase Chain Reaction
Small Interfering RNA
Western Blotting
Neoplasm Metastasis
Technology
Phenotype

Keywords

  • disabled-2
  • EMT
  • MAPK
  • TGFβ

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Disabled-2 downregulation promotes epithelial-to-mesenchymal transition. / Martin, J. C.; Herbert, Brittney-Shea; Hocevar, B. A.

In: British Journal of Cancer, Vol. 103, No. 11, 23.11.2010, p. 1716-1723.

Research output: Contribution to journalArticle

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