1: Oncogene. 2004 Oct 7;23(46):7669-78. 

Mutation of GATA3 in human breast tumors.

Usary J, Llaca V, Karaca G, Presswala S, Karaca M, He X, Langerod A, Karesen R,
Oh DS, Dressler LG, Lonning PE, Strausberg RL, Chanock S, Borresen-Dale AL,
Perou CM.

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel
Hill, NC 27599, USA.

GATA3 is an essential transcription factor that was first identified as a
regulator of immune cell function. In recent microarray analyses of human breast
tumors, both normal breast luminal epithelium and estrogen receptor
(ESR1)-positive tumors showed high expression of GATA3. We sequenced genomic DNA
from 111 breast tumors and three breast-tumor-derived cell lines and identified
somatic mutations of GATA3 in five tumors and the MCF-7 cell line. These
mutations cluster in the vicinity of the highly conserved second zinc-finger
that is required for DNA binding. In addition to these five, we identified using
cDNA sequencing a unique mis-splicing variant that caused a frameshift mutation.
One of the somatic mutations we identified was identical to a germline GATA3
mutation reported in two kindreds with HDR syndrome/OMIM #146255, which is an
autosomal dominant syndrome caused by the haplo-insufficiency of GATA3. The
ectopic expression of GATA3 in human 293T cells caused the induction of 73 genes
including six cytokeratins, and inhibited cell line doubling times. These data
suggest that GATA3 is involved in growth control and the maintenance of the
differentiated state in epithelial cells, and that GATA3 variants may contribute
to tumorigenesis in ESR1-positive breast tumors.

PMID: 15361840 [PubMed - indexed for MEDLINE]


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2: Mol Cell Endocrinol. 2004 Apr 30;219(1-2):1-7. 

About GATA3, HNF3A, and XBP1, three genes co-expressed with the oestrogen
receptor-alpha gene (ESR1) in breast cancer.

Lacroix M, Leclercq G.

Laboratoire Jean-Claude Heuson de Cancerologie Mammaire, Institut Jules Bordet,
Universite Libre de Bruxelles, 127 Boulevard de Waterloo, B-1000 Bruxelles,
Belgium. marc.lacroix@ulb.ac.be

In breast tumours and breast cancer cell (BCC) lines, microarray analyses have
revealed that a series of genes are expressed in close association with the
oestrogen receptor-alpha (ER-alpha) gene, ESR1. Three of them, GATA3, HNF3A
(also known as FOXA1), and XBP1 encode transcription factors. Here, we present
these factors and we discuss their potential involvement in the
ER-alpha-mediated actions in BCC. We notably show the relations that exist, or
that might exist, between these factors and the oestrogen-inducible trefoil
factor TFF1. Copyright 2004 Elsevier Ltd.

PMID: 15149721 [PubMed - indexed for MEDLINE]


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