GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells

Introduction Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been...

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Autores principales: Abba, Martín Carlos, Nunez, María I., Colussi, Andrea G., Croce, María Virginia, Segal-Eiras, Amada, Aldaz, C. Marcelo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2006
Materias:
Ciencias Médicas
MUC1
Factor de Transcripción GATA3
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83469
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-83469
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
MUC1
Factor de Transcripción GATA3
spellingShingle Ciencias Médicas
MUC1
Factor de Transcripción GATA3
Abba, Martín Carlos
Nunez, María I.
Colussi, Andrea G.
Croce, María Virginia
Segal-Eiras, Amada
Aldaz, C. Marcelo
GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
topic_facet Ciencias Médicas
MUC1
Factor de Transcripción GATA3
description Introduction Recent studies have demonstrated that members of the GATA-binding protein (GATA) family (GATA4 and GATA5) might have pivotal roles in the transcriptional upregulation of mucin genes (MUC2, MUC3 and MUC4) in gastrointestinal epithelium. The zinc-finger GATA3 transcription factor has been reported to be involved in the growth control and differentiation of breast epithelial cells. In SAGE (serial analysis of gene expression) studies we observed an intriguing significant correlation between GATA3 and MUC1 mRNA expression in breast carcinomas. We therefore designed the present study to elucidate whether MUC1 expression is regulated by GATA3 in breast cancer cells. Methods: Promoter sequence analysis of the MUC1 gene identified six GATA cis consensus elements in the 5′ flanking region (GATA1, GATA3 and four GATA-like sequences). Chromatin immunoprecipitation and electrophoretic mobility-shift assays were employed to study the presence of a functional GATA3-binding site. GATA3 and MUC1 expression was analyzed in vitro with a GATA3 knockdown assay. Furthermore, expression of GATA3 and MUC1 genes was analyzed by realtime RT-PCR and immunohistochemistry on breast cancer-specific tissue microarrays. Results: We confirmed the presence of a functional GATA3-binding site on the MUC1 promoter region in the MCF7 cell line. We determined that GATA3 knockdown assays led to a decrease in MUC1 protein expression in MCF7 and T47D cells. In addition, we detected a statistically significant correlation in expression between GATA3 and MUC1 genes at the mRNA and protein levels both in normal breast epithelium and in breast carcinomas (p = 0.01). GATA3 expression was also highly associated with estrogen receptor and progesterone receptor status (p = 0.0001) and tumor grade (p = 0.004) in breast carcinomas. Conclusion: Our study provides evidence indicating that GATA3 is probably a mediator for the transcriptional upregulation of MUC1 expression in some breast cancers.
format Articulo
Articulo
author Abba, Martín Carlos
Nunez, María I.
Colussi, Andrea G.
Croce, María Virginia
Segal-Eiras, Amada
Aldaz, C. Marcelo
author_facet Abba, Martín Carlos
Nunez, María I.
Colussi, Andrea G.
Croce, María Virginia
Segal-Eiras, Amada
Aldaz, C. Marcelo
author_sort Abba, Martín Carlos
title GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
title_short GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
title_full GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
title_fullStr GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
title_full_unstemmed GATA3 protein as a MUC1 transcriptional regulator in breast cancer cells
title_sort gata3 protein as a muc1 transcriptional regulator in breast cancer cells
publishDate 2006
url http://sedici.unlp.edu.ar/handle/10915/83469
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bdutipo_str Repositorios
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