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Journal of Mammary Gland Biology and Neoplasia
Published in: Journal of Mammary Gland Biology and Neoplasia 3/2019

01-09-2019 | Breast Cancer

GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice

Authors: Lisette M. Cornelissen, Roebi de Bruijn, Linda Henneman, Yongsoo Kim, Wilbert Zwart, Jos Jonkers

Published in: Journal of Mammary Gland Biology and Neoplasia | Issue 3/2019

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Abstract

Heterozygous mutations in the transcription factor GATA3 are identified in 10–15% of all breast cancer cases. Most of these are protein-truncating mutations, concentrated within or downstream of the second GATA-type zinc-finger domain. Here, we investigated the functional consequences of expression of two truncated GATA3 mutants, in vitro in breast cancer cell lines and in vivo in the mouse mammary gland. We found that the truncated GATA3 mutants display altered DNA binding activity caused by preferred tethering through FOXA1. In addition, expression of the truncated GATA3 mutants reduces E-cadherin expression and promotes anchorage-independent growth in vitro. However, we could not identify any effects of truncated GATA3 expression on mammary gland development or mammary tumor formation in mice. Together, our results demonstrate that both truncated GATA3 mutants promote cistromic re-programming of GATA3 in vitro, but these mutants are not sufficient to induce tumor formation in mice.
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Metadata
Title
GATA3 Truncating Mutations Promote Cistromic Re-Programming In Vitro, but Not Mammary Tumor Formation in Mice
Authors
Lisette M. Cornelissen
Roebi de Bruijn
Linda Henneman
Yongsoo Kim
Wilbert Zwart
Jos Jonkers
Publication date
01-09-2019
Publisher
Springer US
Published in
Journal of Mammary Gland Biology and Neoplasia / Issue 3/2019
Print ISSN: 1083-3021
Electronic ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-019-09432-4

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