Overexpression of the Ets-1 transcription factor in human breast cancer

Buggy, Y.; Maguire, Teresa; McGreal, G.; McDermott, Enda; Hill, A. D. K.; O’Higgins, N.; Duffy, Michael J.

doi:10.1038/sj.bjc.6602128

Cited by 59 publications

(53 citation statements)

References 36 publications

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“…For example, Ets1 and Ets2 expression was reportedly elevated in breast tumors. [25][26][27] However, we identified no consistent change in the Ets2 transcript level and found that the Ets1 transcript level was instead lower in breast cancer cells than in normal breast epithelial cells. We showed that this decreased Ets1 expression occurred not only in cell lines, but also in primary breast cancers (Fig.…”

Section: Discussionmentioning

confidence: 57%

Profile of Ets gene expression in human breast carcinoma

Pan

Hu³

et al. 2007

Cancer Biology & Therapy

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Background: Ets genes encode a family of transcription factors that play key roles in cell proliferation, differentiation and apoptosis. Fusions of Ets genes with other targets have been described in Ewing's sarcoma, chronic myelomonocytic leukemia and more recently prostate carcinoma. Ets expression in breast carcinoma has not been comprehensively studied, and is the focus of this study.Methods: RT-Q-PCR was used to determine the expression of Ets genes in a panel of ten common breast cancer cell lines, two immortalized normal breast epithelial cell lines, and one primary culture of human mammary epithelial cells. Ets with altered expression in cancer cell lines were verified in primary breast tumors.Results: Transcripts of 21 of the 27 Ets genes were detected in either normal or cancer cells. Of the 21 detectable genes, 14 were expressed at a similar level in both normal and breast cancer cell lines. Four genes, Ehf, Elf3, Elf5 and Pdef, were expressed at higher levels in breast cancer cells than normal epithelials. Surprisingly, the expression of Elk3, Ets1 and Fli1 was repressed in breast cancer cells. The protein status of Ehf, Elf3, Pdef, Elk3, Ets1 and Fli1, strongly correlated with the transcript data, suggesting that Ets expression is regulated primarily at the transcriptional level. Similarly, Elf3, Pdef and Tel2 were overexpressed, while Elk3, Ets1 and Fli1 were under-expressed in primary breast tumor specimens in comparison with normal mammary tissues.Conclusions: Our study identified a subset of Ets genes with altered expression in breast carcinoma, implicating their roles in mammary tumorigenesis. While the Ets overexpression pattern is useful to uncover recurrent genetic alterations involving Ets genes, the repressed expression of several Ets genes suggests that some Ets proteins may play suppressor roles during breast cancer progression. Our results warrant detailed studies of individual Ets activity during mammary gland neoplasia.

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Section: Discussionmentioning

confidence: 57%

Profile of Ets gene expression in human breast carcinoma

Pan

Hu³

et al. 2007

Cancer Biology & Therapy

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“…The expression of Ets-1 has been identified in various neoplasms including lung carcinoma (Bolon et al 1995), stomach (Nakayama et al 1996;Yu et al 2003), pancreas (Ito et al 1998), liver (Ozaki et al 2000), esophagus (Saeki et al 2000), ovary (Davidson et al 2001), breast (Buggy et al 2004;Katayama et al 2005), tongue (Endo et al 2006), and prostate (Alipov et al 2005). In these studies, it was speculated that Ets-1 might be involved not only in tumor invasion but also in remodeling of connective tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported the correlation of Ets-1 expression with invasiveness in various solid tumors such as breast carcinoma (Buggy et al 2004;Katayama et al 2005), prostatic carcinoma (Alipov et al 2005), tongue carcinoma (Endo et al 2006), and also with poor prognosis (Davidson et al 2001;Wilson et al 2004). Ets-1 expression was also reported to correlate with tumor progression in patients with non-small cell lung carcinoma (Bolon et al 1995;Sasaki et al 2001;Takanami et al 2001).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Ets-1 Proto-Oncogene as a Potential Predictor for Poor Prognosis of Lung Adenocarcinoma

Yamaguchi

Nakayama

Nanashima

et al. 2007

Tohoku J. Exp. Med.

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The protooncogene Ets-1 is a transcription factor that is known to regulate certain matrix metalloproteinases and plasminogen activator, which have been associated with malignant behaviors in solid carcinomas. We hypothesized that Ets-1 expression is also associated with tumor progression and a worse prognosis in lung carcinoma patients. To clarify the role of the Ets-1 proto-oncogene, the expression of Ets-1 in non-small cell lung carcinomas using 156 paraffin-embedded specimens was determined in surgically resected tissue samples. Immunohistochemical staining showed Ets-1 expression in 82 cases of 156 carcinomas (53%): 36 of 52 (69%) squamous cell carcinomas, 41 of 96 (43%) adenocarcinomas, and 5 of 8 (63%) other carcinomas. In adenocarcinomas, a higher proportion of acinar type expressed Ets-1 compared to papillary or alveolar type ( p < 0.05). The proportion of adenocarcinoma that expressed Ets-1 increased with poorer histologic differentiation of the adenocarcinoma ( p < 0.05). Ets-1 positive adenocarcinomas had a larger mean size than Ets-1 negative adenocarcinomas ( p < 0.01). In adenocarcinoma patients, expression of Ets-1 was associated with disease-free ( p = 0.09) and overall survivals ( p < 0.05) after lung resection. Such relationship was not observed among squamous cell carcinoma patients. Our findings indicate that Ets-1 expression is related to histopathological differentiation, morphogenesis, and tumor progression of lung adenocarcinomas. Ets-1 appears to be a useful predictor of poor prognosis after surgical resection in lung adenocarcinoma patients. Ets-1 expression could be used to evaluate the malignant behaviors of lung adenocarcinomas.Ets-1; non-small cell lung cancer; histologic differentiation; subtype; prognosis

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“…ETS1 and ETS2 have been implicated in the increased expression of uPA and a subsequent increase in the migratory ability of cancer cells (Watabe et al, 1998;Nakada et al, 1999;Behrens et al, 2001;Buggy et al, 2004;Buggy et al, 2006). Significantly, the specific EBS occupied by PDEF was originally identified as a regulatory element for the ETS transcription factor PEA3, and its expression has been shown to increase uPA promoter activity (D'Orazio et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…Significantly, ETS factors are known to both positively and negatively regulate the migratory phenotype, depending on the family member expressed and the context of expression (Turner et al, 2007a;Turner and Watson, 2008). In breast and other solid tumors, the increased expression of ETS1 and ETS2 (Watabe et al, 1998;Behrens et al, 2001;Buggy et al, 2004Buggy et al, , 2006 as well as PEA3 (Benz et al, 1997;Bosc et al, 2001;Bieche et al, 2004) is associated with increased metastatic potential and an increased ability for motile function through the altered expression of regulatory target genes known to mediate cytoskeletal changes. Prostate derived ETS factor (PDEF) is an epithelial specific ETS family member that is associated with the negative regulation of metastatic potential (Feldman et al, 2003;Ghadersohi et al, 2006;Gu et al, 2007;Turner et al, 2007b).…”

Section: Introductionmentioning

confidence: 99%

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

Turner

Findlay

Kirven

et al. 2008

MBoC

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Prostate derived ETS factor (PDEF) is an ETS (epithelial-specific E26 transforming sequence) family member that has been identified as a potential tumor suppressor. In multiple invasive breast cancer cells, PDEF expression inhibits cell migration by preventing the acquisition of directional morphological polarity conferred by changes in cytoskeleton organization. In this study, microarray analysis was used to identify >200 human genes that displayed a common differential expression pattern in three invasive breast cancer cell lines after expression of exogenous PDEF protein. Gene ontology associations and data mining analysis identified focal adhesion, adherens junctions, cell adhesion, and actin cytoskeleton regulation as cell migration-associated interaction pathways significantly impacted by PDEF expression. Validation experiments confirmed the differential expression of four cytoskeleton-associated genes with known functional associations with these pathways: uPA, uPAR, LASP1, and VASP. Significantly, chromatin immunoprecipitation studies identified PDEF as a direct negative regulator of the metastasis-associated gene uPA and phenotypic rescue experiments demonstrate that exogenous urokinase plasminogen activator (uPA) expression can restore the migratory ability of invasive breast cancer cells expressing PDEF. Furthermore, immunofluorescence studies identify the subcellular relocalization of urokinase plasminogen activator receptor (uPAR), LIM and SH3 protein (LASP1), and vasodilatorstimulated protein (VASP) as a possible mechanism accounting for the loss of morphological polarity observed upon PDEF expression.

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Overexpression of the Ets-1 transcription factor in human breast cancer

Cited by 59 publications

References 36 publications

Profile of Ets gene expression in human breast carcinoma

Profile of Ets gene expression in human breast carcinoma

Ets-1 Proto-Oncogene as a Potential Predictor for Poor Prognosis of Lung Adenocarcinoma

Global Gene Expression Analysis Identifies PDEF Transcriptional Networks Regulating Cell Migration during Cancer Progression

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