Arsenic reduces the GATA3 expression associated with an increase in proliferation and migration of mammary epithelial cell line MCF-10A
Copyright © 2023 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:472 |
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| Enthalten in: |
Toxicology and applied pharmacology - 472(2023) vom: 01. Aug., Seite 116573 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vergara-Gerónimo, Cristian A [VerfasserIn] |
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| Links: |
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| Themen: |
Arsenic |
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| Anmerkungen: |
Date Completed 07.09.2023 Date Revised 23.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.taap.2023.116573 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Arsenic | |
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| 700 | 1 | |a Camacho-Carranza, Rafael |e verfasserin |4 aut | |
| 700 | 1 | |a Ostrosky-Wegman, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Salazar, Ana María |e verfasserin |4 aut | |
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