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

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.

• Authors: Lisette M Cornelissen, Roebi de Bruijn, Linda Henneman, Yongsoo Kim, Wilbert Zwart, Jos Jonkers
• Journal: Journal of mammary gland biology and neoplasia (J Mammary Gland Biol Neoplasia) Vol. 24 Issue 3 Pg. 271-284 (09 2019) ISSN: 1573-7039 [Electronic] United States
• PMID: 31218575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• FOXA1 protein, human
• Foxa1 protein, mouse
• GATA3 Transcription Factor
• GATA3 protein, human
• Hepatocyte Nuclear Factor 3-alpha

Topics

• Animals
• Apoptosis
• Breast Neoplasms (genetics, metabolism, pathology)
• Cadherins (genetics, metabolism)
• Cell Adhesion
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Cellular Reprogramming
• Female
• GATA3 Transcription Factor (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Hepatocyte Nuclear Factor 3-alpha (metabolism)
• Humans
• In Vitro Techniques
• Mammary Glands, Animal (cytology, metabolism)
• Mammary Neoplasms, Animal (genetics, metabolism, pathology)
• Mice
• Mutation