scholarly journals Cell type-specific properties and environment shape tissue specificity of cancer genes

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Martin H. Schaefer ◽  
Luis Serrano
Keyword(s):  
Tissue Specificity ◽  
Cancer Genes ◽  
Cell Type ◽  
Cell Type Specific

scholarly journals Differential Cell-Specific Modulation of HOXA10 by Estrogen and Specificity Protein 1 Response Elements

2007 ◽  
Vol 92 (5) ◽  
pp. 1920-1926 ◽  
Author(s):  
Ryan Martin ◽  
Melissa B. Taylor ◽  
Graciela Krikun ◽  
Charles Lockwood ◽  
G. Edda Akbas ◽  
...  
Keyword(s):  
Electrophoretic Mobility ◽  
Tissue Specificity ◽  
Academic Medical Center ◽  
Cell Type ◽  
Mobility Shift ◽  
Response Elements ◽  
Specificity Protein 1 ◽  
Cellular Expression ◽  
Cell Type Specific ◽  
Specificity Protein

Abstract Context: HOX genes are highly evolutionarily conserved regulators of embryonic development. HOXA10 also regulates differentiation of the adult reproductive tract and mammary gland in response to sex steroids. Objective: We recently identified two HOXA10 estrogen response elements (EREs). Here we demonstrate that estrogen-responsive HOXA10 expression is cell type specific. Design and Setting: We conducted an in vitro study at an academic medical center. Main Outcome Measure: Reporter assay, gel shift assays (electrophoretic mobility shift assay), and immunohistochemistry were done. Results: The HOXA10 EREs and a specificity protein 1 (Sp1) binding site differentially drive the cell-type-specific E2 response. In electrophoretic mobility shift assays, both estrogen receptor-α and -β bound both EREs but not the Sp1 site. In reporter assays, both EREs and the Sp1 site demonstrated estrogen responsiveness and tissue specificity; transiently transfected uterine Ishikawa cells or breast MCF-7 cells showed differential responses to E2 treatment. Each response element (Sp1, ERE1, and ERE2) drove distinct differential expression in each cell type. Sp1 protein was expressed in a menstrual-cycle stage-specific expression pattern in endometrium, first expressed in perivascular cells. Conclusions: Tissue specificity inherent to a regulatory element as well as differential cellular expression of transcription factors imparts differential tissue-specific estrogen responsiveness.

scholarly journals Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154070 ◽  
Author(s):  
Kathryn L. Gilroy ◽  
Anne Terry ◽  
Asif Naseer ◽  
Jeroen de Ridder ◽  
Amin Allahyar ◽  
...  
Keyword(s):  
Cancer Genomics ◽  
Cancer Genes ◽  
Cell Type ◽  
Specific Cancer ◽  
Cell Type Specific ◽  
Retrovirus Integration

scholarly journals Localization of a repressive sequence contributing to B-cell specificity in the immunoglobulin heavy-chain enhancer.

1988 ◽  
Vol 8 (2) ◽  
pp. 988-992 ◽  
Author(s):  
J Weinberger ◽  
P S Jat ◽  
P A Sharp
Keyword(s):  
Heavy Chain ◽  
Tissue Specificity ◽  
Immunoglobulin Heavy Chain ◽  
Cell Type ◽  
Cis Acting ◽  
Lymphoid Lineage ◽  
Cell Specificity ◽  
Cell Type Specific ◽  
Minimal Sequences ◽  
Repressor Element

The immunoglobulin heavy-chain enhancer is a cis-acting element which activates transcription of nearby genes only in cells of the lymphoid lineage. To identify the minimal sequences necessary to impart cell type transcriptional specificity, we tested the activity of several deletions and internal mutations in the mu enhancer. Experiments involving measurement of both chloramphenicol acetyltransferase activity and RNA levels indicated the presence of a dominant repressor element within the mu enhancer. This repressive activity was detected in fibroblasts but not in myeloma cells. Removal or disruption of this repressor element revealed the presence of elements within the mu enhancer that activate transcription in fibroblasts. Thus, enhancer tissue specificity is in part due to the composite of both constitutive activation and cell-type-specific repressive activity. The possible biological roles of this phenomenon are discussed.

scholarly journals Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Matthew A Mitsche ◽  
Jeffrey G McDonald ◽  
Helen H Hobbs ◽  
Jonathan C Cohen
Keyword(s):  
Tissue Specificity ◽  
Isotope Labeling ◽  
Cultured Cells ◽  
Cholesterol Biosynthesis ◽  
Flux Analysis ◽  
Preputial Gland ◽  
Cell Type ◽  
Isotopomer Analysis ◽  
Cell Type Specific

Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K–R pathway. Rather, a hybrid pathway was identified that we call the modified K–R (MK–R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK–R pathway. Thus, relative use of the Bloch and MK–R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol.

scholarly journals Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Katey S. S. Enfield ◽  
Erin A. Marshall ◽  
Christine Anderson ◽  
Kevin W. Ng ◽  
Sara Rahmati ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Prognostic Value ◽  
Tissue Specificity ◽  
Clinical Evidence ◽  
Gene Dosage ◽  
Cell Type ◽  
Epithelial Tumor ◽  
Subtype Specificity ◽  
Cell Type Specific ◽  
Pan Cancer

AbstractGene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.

Localization of a repressive sequence contributing to B-cell specificity in the immunoglobulin heavy-chain enhancer

1988 ◽  
Vol 8 (2) ◽  
pp. 988-992
Author(s):  
J Weinberger ◽  
P S Jat ◽  
P A Sharp
Keyword(s):  
Heavy Chain ◽  
Tissue Specificity ◽  
Immunoglobulin Heavy Chain ◽  
Cell Type ◽  
Cis Acting ◽  
Lymphoid Lineage ◽  
Cell Specificity ◽  
Cell Type Specific ◽  
Minimal Sequences ◽  
Repressor Element

The immunoglobulin heavy-chain enhancer is a cis-acting element which activates transcription of nearby genes only in cells of the lymphoid lineage. To identify the minimal sequences necessary to impart cell type transcriptional specificity, we tested the activity of several deletions and internal mutations in the mu enhancer. Experiments involving measurement of both chloramphenicol acetyltransferase activity and RNA levels indicated the presence of a dominant repressor element within the mu enhancer. This repressive activity was detected in fibroblasts but not in myeloma cells. Removal or disruption of this repressor element revealed the presence of elements within the mu enhancer that activate transcription in fibroblasts. Thus, enhancer tissue specificity is in part due to the composite of both constitutive activation and cell-type-specific repressive activity. The possible biological roles of this phenomenon are discussed.

IFIH1-deficiency results in a cell-type specific alteration of autophagic activity in response to S. typhimurium

2017 ◽  
Vol 55 (05) ◽  
pp. e28-e56
Author(s):  
S Macheiner ◽  
R Gerner ◽  
A Pfister ◽  
A Moschen ◽  
H Tilg
Keyword(s):  
Cell Type ◽  
A Cell ◽  
Cell Type Specific ◽  
Autophagic Activity ◽  
Specific Alteration
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