Sequencing, Transcript Identification, and Quantitative Gene Expression Profiling in the Breast Cancer Loss of Heterozygosity Region 16q24.3 Reveal Three Potential Tumor-Suppressor Genes

Powell, Jason A.; Gardner, Alison; Bais, Anthony J.; Hinze, Susan J.; Baker, Elizabeth; Whitmore, Scott A.; Crawford, Joanna; Kochetkova, Marina; Spendlove, Hayley E.; Doggett, Norman A.; Sutherland, Grant R.; Callen, David F.; Kremmidiotis, Gabriel

doi:10.1006/geno.2002.6828

Cited by 46 publications

(38 citation statements)

References 40 publications

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“…This was strongly supported by our preliminary experiments conducted on few breast cancer cell lines (MCF-7, HBL-100, and MDA MB 468) as it was observed that SMAR1 expression was reduced at a transcriptional level. 2 Detailed loss of heterozygosity studies in breast tumors has identified three regions of frequent allelic imbalance (54), and further quantitative gene expression profiling in the breast cancer loss of heterozygosity region 16q24.3 reveals three potential tumor-suppressor genes (55). Translocation of the 16q24 may cause disruption of BANP (SMAR1) expression leading to abnormal cell cycle progression through destabilization of p53.…”

Section: Discussionmentioning

confidence: 99%

Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif

Jalota

Singh

Pavithra

et al. 2005

Journal of Biological Chemistry

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Various stresses and DNA-damaging agents trigger transcriptional activity of p53 by post-translational modifications, making it a global regulatory switch that controls cell proliferation and apoptosis. Earlier we have shown that the novel MAR-associated protein SMAR1 interacts with p53. Here we delineate the minimal domain of SMAR1 (the arginine-serine-rich domain) that is phosphorylated by protein kinase C family proteins and is responsible for p53 interaction, activation, and stabilization within the nucleus. SMAR1-mediated stabilization of p53 is brought about by inhibiting Mdm2-mediated degradation of p53. We also demonstrate that this arginine-serine (RS)-rich domain triggers the various cell cycle modulating proteins that decide cell fate. Furthermore, phenotypic knock-down experiments using small interfering RNA showed that SMAR1 is required for activation and nuclear retention of p53. The level of phosphorylated p53 was significantly increased in the thymus of SMAR1 transgenic mice, showing in vivo significance of SMAR1 expression. This is the first report that demonstrates the mechanism of action of the MAR-binding protein SMAR1 in modulating the activity of p53, often referred to as the "guardian of the genome."

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Section: Discussionmentioning

confidence: 99%

Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif

Jalota

Singh

Pavithra

et al. 2005

Journal of Biological Chemistry

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“…Therefore, it is reasonable to speculate that ANCO-1 may serve as a molecular marker for the tumors. The ANCO-1 gene is located at 16q24.3, a region that is frequently deleted in cancer (34,38). This finding supports the possibility that ANCO-1 may be a cancerrelated gene.…”

Section: Discussionsupporting

confidence: 61%

Identification of a Novel Family of Ankyrin Repeats Containing Cofactors for p160 Nuclear Receptor Coactivators

Zhang

Yeung

et al. 2004

Journal of Biological Chemistry

111

112

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Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators. It encodes a large nuclear protein with five ankyrin repeats, and parts of its sequences have been reported as nasopharyngeal carcinoma susceptibility protein and medulloblastoma antigen. Immunofluorescence staining reveals discrete nuclear foci of ANCO-1 that are distinct from known nuclear structures. Intriguingly, ANCO-1 also colocalizes and interacts with histone deacetylases. Transient reporter gene assay shows that ANCO-1 expression inhibits ligand-dependent transactivation by both steroid and nonsteroid nuclear receptors. Taken together, we have identified a novel family of ankyrin repeats containing cofactors that may recruit histone deacetylases to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.

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“…Recent evidence [46-48] revealed that the active immune phagocytosis pathway could inhibit tumor growth through phagocytic clearance, i.e., programmed cell removal in clearing damaged and foreign cells. The CYBA gene is a tumor suppressor [49], which regulates the immune system cells - phagocytes, involved in autophagy. The phagocytosis and superoxide production is primary regulated by the cytochrome b- 245, (light) alpha subunit (also known as p 22 phox ), which is encoded by the gene CYBA.…”

Section: Resultsmentioning

confidence: 99%

Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression

Gong

Clarke

2014

BMC Systems Biology

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BackgroundRecent global genomic analyses identified 69 gene sets and 12 core signaling pathways genetically altered in pancreatic cancer, which is a highly malignant disease. A comprehensive understanding of the genetic signatures and signaling pathways that are directly correlated to pancreatic cancer survival will help cancer researchers to develop effective multi-gene targeted, personalized therapies for the pancreatic cancer patients at different stages. A previous work that applied a LASSO penalized regression method, which only considered individual genetic effects, identified 12 genes associated with pancreatic cancer survival.ResultsIn this work, we integrate pathway information into pancreatic cancer survival analysis. We introduce and apply a doubly regularized Cox regression model to identify both genes and signaling pathways related to pancreatic cancer survival.ConclusionsFour signaling pathways, including Ion transport, immune phagocytosis, TGFβ (spermatogenesis), regulation of DNA-dependent transcription pathways, and 15 genes within the four pathways are identified and verified to be directly correlated to pancreatic cancer survival. Our findings can help cancer researchers design new strategies for the early detection and diagnosis of pancreatic cancer.

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Sequencing, Transcript Identification, and Quantitative Gene Expression Profiling in the Breast Cancer Loss of Heterozygosity Region 16q24.3 Reveal Three Potential Tumor-Suppressor Genes

Cited by 46 publications

References 40 publications

Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif

Tumor Suppressor SMAR1 Activates and Stabilizes p53 through Its Arginine-Serine-rich Motif

Identification of a Novel Family of Ankyrin Repeats Containing Cofactors for p160 Nuclear Receptor Coactivators

Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression

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