Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells

E. A. Burwell, G. P. McCarty, L. A. Simpson, K. A. Thompson, D. M. Loeb

Research output: Contribution to journalArticle

Abstract

The role of WT1 (Wilm's tumor suppressor gene) in breast cancer is controversial, with evidence for both tumor-promoting and tumor-suppressing activities. In order to address this question, we expressed different WT1 isoforms in the mammary epithelial cell line H16N-2, which does not express endogenous WT1. Cells were stably transfected with either WT1 (-Ex5/-KTS) or WT1 (+Ex5/+KTS) under the control of the inducible metallothionein promoter. Induction of WT1 (-Ex5/-KTS) upregulated p21, causing a slowing of proliferation and a G2-phase cell cycle arrest. In artificial basement membrane, the WT1 (-Ex5/-KTS) isoform promoted the appearance of highly organized acinar cellular aggregates. In contrast, WT1 (+Ex5/+KTS) had no effect on p21 or proliferation, but rather caused an epithelial-mesenchymal transition and a redistribution of E-cadherin from the cell membrane to the cytoplasm. This isoform also causes the cellular aggregates growing in artificial basement membrane to appear significantly less organized than control cells. Thus, different WT1 isoforms have distinct effects in this cell line, suggesting that depending on the ratio of WT1 isoform expression in mammary epithelial cells, WT1 could function to either promote or suppress a transformed phenotype.

Original languageEnglish (US)
Pages (from-to)3423-3430
Number of pages8
JournalOncogene
Volume26
Issue number23
DOIs
StatePublished - May 17 2007

Fingerprint

Wilms' Tumor Genes
Tumor Suppressor Genes
Protein Isoforms
Breast
Epithelial Cells
Artificial Membranes
Basement Membrane
G2 Phase Cell Cycle Checkpoints
Cell Line
Epithelial-Mesenchymal Transition
Metallothionein
G2 Phase
Cadherins
Neoplasms
Cytoplasm
Cell Membrane
Breast Neoplasms
Phenotype

Keywords

  • Alternative splicing
  • Breast cancer
  • Cell cycle
  • Epithelial-mesenchymal transition
  • Oncogene

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Burwell, E. A., McCarty, G. P., Simpson, L. A., Thompson, K. A., & Loeb, D. M. (2007). Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells. Oncogene, 26(23), 3423-3430. https://doi.org/10.1038/sj.onc.1210127

Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells. / Burwell, E. A.; McCarty, G. P.; Simpson, L. A.; Thompson, K. A.; Loeb, D. M.

In: Oncogene, Vol. 26, No. 23, 17.05.2007, p. 3423-3430.

Research output: Contribution to journalArticle

Burwell, EA, McCarty, GP, Simpson, LA, Thompson, KA & Loeb, DM 2007, 'Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells', Oncogene, vol. 26, no. 23, pp. 3423-3430. https://doi.org/10.1038/sj.onc.1210127
Burwell, E. A. ; McCarty, G. P. ; Simpson, L. A. ; Thompson, K. A. ; Loeb, D. M. / Isoforms of Wilms' tumor suppressor gene (WT1) have distinct effects on mammary epithelial cells. In: Oncogene. 2007 ; Vol. 26, No. 23. pp. 3423-3430.
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