GATA-3 Expression as a Predictor of Hormone Response in Breast Cancer

Parikh, Purvi; Palazzo, Juan; Rose, Lewis J.; Daskalakis, Constantine; Weigel, Ronald J.

doi:10.1016/j.jamcollsurg.2004.12.025

Cited by 69 publications

(51 citation statements)

References 26 publications

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“…In a previous pilot study of 28 ER-positive patients who had received hormone treatment, we found that GATA3-positive tumors had almost 90% lower risk of being hormone unresponsive than GATA3-negative tumors [13]. Our current study included 121 ER-positive patients, of whom 46 had received hormone therapy.…”

Section: Discussionmentioning

confidence: 89%

“…However, approximately 30 % of ER-positive breast cancers do not respond to hormonal therapy. In breast cancer, it has been shown that higher expression of GATA3 predicts a better prognosis and GATA3 expression has been shown to be a predictor of hormonal response [13][14][15]. The goal of this study is to correlate GATA3 expression with recurrence and survival in ER-positive breast cancer patients with 10 years of follow-up.…”

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confidence: 99%

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The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Ciocca¹,

Daskalakis²,

Ciocca³

et al. 2009

Human Pathology

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Ciocca¹,

Daskalakis²,

Ciocca³

et al. 2009

Human Pathology

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“…Analysis of 115 breast tumor samples confirmed that expression of GATA3 correlated with the expression of a subset of genes considered important in breast luminal epithelial function (Sorlie et al, 2003). Importantly, the highest expression of GATA3 and ESR1 is seen in tumors of the 'luminal A' subtype, which is associated with the most favorable survival outcomes (Parikh et al, 2005). The lower expression of GATA3 and ESR1 is characteristic of the 'luminal B' ER þ subtype, which is associated with poor survival; the lowest expression of GATA3 is seen in 'HER2 þ ' and 'basal-like' tumor subtypes, which show the worst outcomes (Sorlie et al, 2003;Mehra et al, 2005;Parikh et al, 2005).…”

mentioning

confidence: 86%

“…Importantly, the highest expression of GATA3 and ESR1 is seen in tumors of the 'luminal A' subtype, which is associated with the most favorable survival outcomes (Parikh et al, 2005). The lower expression of GATA3 and ESR1 is characteristic of the 'luminal B' ER þ subtype, which is associated with poor survival; the lowest expression of GATA3 is seen in 'HER2 þ ' and 'basal-like' tumor subtypes, which show the worst outcomes (Sorlie et al, 2003;Mehra et al, 2005;Parikh et al, 2005). Somatic mutations of GATA3 have been identified in five breast tumors (and not in 192 control individuals (388 chromosomes)) (Usary et al, 2004).…”

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confidence: 99%

Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression

2007

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The critical role for GATA family proteins in maintaining the normal (non-transformed) cell state is corroborated by the recent findings of mutations or methylation in GATA genes both in primary cancers and tumor lines including breast. Previously, microarray profiling studies determined that the highest expression of both GATA3 and ESR1 (estrogen receptor a) is seen in tumors associated with the most favorable survival outcomes, whereas the lowest expression of GATA3 is detected in tumor subtypes showing the worst outcomes. At this time, genes and pathways that are regulated by GATA3 in the mammary gland are not well defined. We have previously established a requirement for FOG (Friend Of GATA) cofactors during mouse development. Here we report that in the murine mammary gland Fog2 gene expression is upregulated upon pregnancy and lactation with prominent expression in the epithelial cells of the gland during post-lactational regression. Mammary-specific deletion of Fog2 identified a role for this gene during gland involution; excision of the Fog2 gene leads to the accelerated involution of the gland despite diminished levels of the remodeling enzymes. Importantly, the levels of several genes linked to the control of cancerous transformation in the breast (Esr1, Prg and Foxa1) are significantly reduced upon Fog2 excision. This implicates FOG2 in the maintenance of epithelial cell differentiation in the mammary gland and in performing a protective role in breast cancer.

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“…GATA3 as a marker of breast cancer progression GATA3 and ER are part of a positive regulatory loop (Eeckhoute et al, 2007) and the loss of GATA3 expression during breast cancer progression is concordantly associated with the downregulation of ER, a classic hallmark of tumor progression and poor prognosis (Parikh et al, 2005;Oh et al, 2006;Voduc et al, 2008). Whether or not GATA3 expression holds prognostic value independently of ER expression is still a matter of debate, as contradictory results have been obtained regarding this issue (Mehra et al, 2005;Voduc et al, 2008).…”

Section: Gata3 In Tumor Growthmentioning

confidence: 99%

GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis

et al. 2009

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The loss of expression of the transcription factor GATA3 in breast tumors has been linked to aggressive tumor development and poor patient survival. In the present work, we address potential roles for GATA3 in breast tumor lung metastasis and progression. Using an aggressive breast cancer cell line, which metastasizes specifically to the lung, we show that GATA3 expression results in reduced tumor outgrowth in the mammary fat pad and lower lung metastatic burden in nude mice. Specifically, GATA3 expression inhibits breast cancer cell expansion inside the lung parenchyma. This phenotype correlates with the ability of GATA3 to negatively regulate the expression of several genes that promote breast cancer lung metastasis (ID1/-3, KRTHB1, LY6E and RARRES3). Conversely, the expression of genes encoding known inhibitors of lung metastasis (DLC1 (deleted in liver cancer 1) and PAEP (progestagen-associated endometrial protein)) is upregulated by GATA3. These data correlate with microarray data from human breast cancer patients, showing a strong correlation between high GATA3 expression and absence of metastases specifically to the lungs. We conclude that GATA3 inhibits primary breast tumor outgrowth and reduces lung metastatic burden by regulating key genes involved in metastatic breast tumor progression.

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GATA-3 Expression as a Predictor of Hormone Response in Breast Cancer

Cited by 69 publications

References 26 publications

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

The significance of GATA3 expression in breast cancer: a 10-year follow-up study

Fog2 excision in mice leads to premature mammary gland involution and reduced Esr1 gene expression

GATA3 inhibits breast cancer growth and pulmonary breast cancer metastasis

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