Related Experiment Video
Updated: Jul 28, 2025
The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
Published on: June 12, 2019
Arsenic reduces the GATA3 expression associated with an increase in proliferation and migration of mammary epithelial
Cristian A Vergara-Gerónimo1, Alfonso León-Del-Rio1, Mauricio Rodríguez-Dorantes2
1Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Apartado Postal 70228, Ciudad de México, Mexico.
Abstract:
Arsenic is associated with the development of breast cancer. However, the molecular mechanisms of arsenic induction of breast cancer are not fully defined. Interaction with zinc finger (ZnF) motifs in proteins is one of the proposed mechanisms of arsenic toxicity. GATA3 is a transcription factor that regulates the transcription of genes associated with cell proliferation, cell differentiation and the epithelial-mesenchymal transition (EMT) in mammary luminal cells. Given that GATA3 possesses two ZnF motifs essential for the function of this protein and that arsenic could alter the function of GATA3 through interaction with these structural motifs, we evaluated the effect of sodium arsenite (NaAsO2) on GATA3 function and its relevance in the development of arsenic-induced breast cancer. Breast cell lines derived from normal mammary epithelium (MCF-10A), hormone receptor-positive and hormone receptor negative breast cancer cells (T-47D and MDA-MB-453, respectively) were used. We observed a reduction on GATA3 protein levels at non-cytotoxic concentrations of NaAsO2 in MCF-10A and T-47D, but not in MDA-MB-453 cells. This reduction was associated with an increase in cell proliferation and cell migration in MCF-10A, but not in T-47D or MDA-MB-453 cells. The evaluation of cell proliferation and EMT markers indicate that the reduction on GATA3 protein levels by arsenic, disrupts the function of this transcription factor. Our data indicate that GATA3 is a tumor suppressor in the normal mammary epithelium and that arsenic could act as an initiator of breast cancer by disrupting the function of GATA3.
Insights
Arsenic exposure reduces GATA3 levels, a tumor suppressor, in breast cells. This disruption promotes cell proliferation and migration, suggesting arsenic may initiate breast cancer by impairing GATA3 function.
Area of Science:
- Environmental Health
- Molecular Biology
- Oncology
Background:
- Arsenic exposure is linked to breast cancer, but mechanisms remain unclear.
- Arsenic toxicity may involve interactions with zinc finger (ZnF) motifs in proteins.
- GATA3, a transcription factor with ZnF motifs, regulates mammary cell functions.
Purpose of the Study:
- To investigate the effect of sodium arsenite (NaAsO2) on GATA3 function.
- To determine the role of GATA3 disruption in arsenic-induced breast cancer development.
Main Methods:
- Utilized normal (MCF-10A) and breast cancer cell lines (T-47D, MDA-MB-453).
- Assessed GATA3 protein levels, cell proliferation, and migration after NaAsO2 treatment.
- Evaluated epithelial-mesenchymal transition (EMT) markers.
Main Results:
- NaAsO2 reduced GATA3 protein levels in MCF-10A and T-47D cells at non-cytotoxic concentrations.
- Reduced GATA3 was associated with increased proliferation and migration in MCF-10A cells.
- Arsenic-induced reduction of GATA3 disrupted its tumor suppressor function.
Conclusions:
- GATA3 acts as a tumor suppressor in normal mammary epithelium.
- Arsenic may initiate breast cancer by disrupting GATA3 function through its ZnF motifs.
