Identification of genes induced by BRCA1 in breast cancer cells

Atalay, Arzu; Crook, Tim; Öztürk, Mehmet; Yuluğ, Işık G.

doi:10.1016/s0006-291x(02)02751-1

Cited by 39 publications

(40 citation statements)

References 117 publications

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“…Previous studies have demonstrated that Erbin is a target of the tumor suppressor BRCA-1 and that loss of BRCA-1 and Erbin mRNA expression are correlated with a poor prognosis in early primary breast cancer (46,47). Erbin expression is also increased at the neuromuscular junction after denervation, suggesting that the protein levels of Erbin are regulated by neuronal activity (25).…”

Section: Discussionmentioning

confidence: 99%

A Role for Erbin in the Regulation of Nod2-dependent NF-κB Signaling

McDonald

Chen

Ollendorff

et al. 2005

Journal of Biological Chemistry

168

157

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Nod2 is an intracellular sensor of a specific bacterial cell wall component, muramyl dipeptide, and activation of Nod2 stimulates an inflammatory response. Specific mutations of Nod2 have been associated with two inflammatory diseases, Crohn disease and Blau syndrome, and are thought to contribute to disease susceptibility through altering Nod2 signaling. Association of disease with inappropriate activation of Nod2 highlights the importance of proper regulation of Nod2 activity. However, little is known about specific regulation of the Nod2 pathway. We performed a biochemical screen to discover potential regulators of Nod2 and identified Erbin, a protein involved in cell polarity, receptor localization, and regulation of the mitogen-activated protein kinase pathway, as a novel Nod2-interacting protein. In our studies, we demonstrate specific interaction of Erbin and Nod2 both in vitro and in vivo and characterize the regions required for interaction in both proteins. We found that Nod2-dependent activation of NF-B and cytokine secretion is inhibited by Erbin overexpression, whereas Erbin ؊/؊ mouse embryo fibroblasts show an increased sensitivity to muramyl dipeptide. These studies identify Erbin as a regulator of Nod2 signaling and demonstrate a novel role for Erbin in inflammatory responses.

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Section: Discussionmentioning

confidence: 99%

A Role for Erbin in the Regulation of Nod2-dependent NF-κB Signaling

McDonald

Chen

Ollendorff

et al. 2005

Journal of Biological Chemistry

168

157

View full text Add to dashboard Cite

show abstract

“…Poly(A)+ RNA was subsequently isolated using Poly(A)+ spin columns (New England Biolabs). Subtraction PCR was performed with 2 μg poly(A)+ RNA for tester and driver using the PCR select system (Clontech), with the modifications previously described (55).…”

Section: Methodsmentioning

confidence: 99%

Epigenetic downregulation of human disabled homolog 2 switches TGF-β from a tumor suppressor to a tumor promoter

Hannigan¹,

Smith²,

Kalna³

et al. 2010

J. Clin. Invest.

Self Cite

100

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The cytokine TGF-β acts as a tumor suppressor in normal epithelial cells and during the early stages of tumorigenesis. During malignant progression, cancer cells can switch their response to TGF-β and use this cytokine as a potent oncogenic factor; however, the mechanistic basis for this is poorly understood. Here we demonstrate that downregulation of disabled homolog 2 (DAB2) gene expression via promoter methylation frequently occurs in human squamous cell carcinomas (SCCs) and acts as an independent predictor of metastasis and poor prognosis. Retrospective microarray analysis in an independent data set indicated that low levels of DAB2 and high levels of TGFB2 expression correlate with poor prognosis. Immunohistochemistry, reexpression, genetic knockout, and RNAi silencing studies demonstrated that downregulation of DAB2 expression modulated the TGF-β/Smad pathway. Simultaneously, DAB2 downregulation abrogated TGF-β tumor suppressor function, while enabling TGF-β tumor-promoting activities. Downregulation of DAB2 blocked TGF-β-mediated inhibition of cell proliferation and migration and enabled TGF-β to promote cell motility, anchorage-independent growth, and tumor growth in vivo. Our data indicate that DAB2 acts as a tumor suppressor by dictating tumor cell TGF-β responses, identify a biomarker for SCC progression, and suggest a means to stratify patients with advanced SCC who may benefit clinically from anti-TGF-β therapies.

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“…Recently, OVCA1 has been identified as a BRCA1-inducible gene, using a forced BRCA1 overexpression assay in the MCF breast cancer cell line (Atalay et al 2002). BRCA1 mutations are associated with the formation of both breast and ovarian cancer (Gayther et al 1995).…”

Section: Genes and Development 327mentioning

confidence: 99%

Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis

Chen¹,

Behringer²

2004

Genes Dev.

102

112

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Loss of OVCA1/DPH2L1 correlates with ovarian and breast cancer. To study its in vivo role, we generated Ovca1 mutant alleles in mice. Ovca1 heterozygotes spontaneously develop cancer. Ovca1 mutant mice die during embryonic development and at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Ovca1 mutant mouse embryonic fibroblasts (MEFs). p53 deficiency can rescue these Ovca1 mutant MEF proliferation defects and partially rescue Ovca1 mutant embryonic phenotypes. Furthermore, Ovca1; p53 double heterozygotes developed tumors quicker than p53 heterozygotes and with an increased carcinoma incidence. Multiple tumor burden in Ovca1 heterozygotes that were also p53 deficient was significantly higher than in p53 homozygous mutants. These in vivo findings demonstrate that Ovca1 is a tumor suppressor that can modify p53-induced tumorigenesis and suggest that it acts as a positive regulator for cell cycle progression. The close linkage of OVCA1 and p53 on human Chromosome 17 suggests that coordinated loss may be an important mechanism for the evolution of ovarian, breast, and other tumor phenotypes.[Keywords: Tumor suppressor; ovarian cancer; DPH2L1; Ovca2; HIC1; Miller-Dieker syndrome] Supplemental material is available at http://www.genesdev.org.

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Identification of genes induced by BRCA1 in breast cancer cells

Cited by 39 publications

References 117 publications

A Role for Erbin in the Regulation of Nod2-dependent NF-κB Signaling

A Role for Erbin in the Regulation of Nod2-dependent NF-κB Signaling

Epigenetic downregulation of human disabled homolog 2 switches TGF-β from a tumor suppressor to a tumor promoter

Ovca1 regulates cell proliferation, embryonic development, and tumorigenesis

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