hes1-protein--human and Carcinoma--Mucoepidermoid

hes1-protein--human has been researched along with Carcinoma--Mucoepidermoid* in 1 studies

Other Studies

1 other study(ies) available for hes1-protein--human and Carcinoma--Mucoepidermoid

Article	Year
t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway. Nature genetics, 2003, Volume: 33, Issue:2 Truncation of Notch1 has been shown to cause a subtype of acute leukemia, and activation of Notch4 has been associated with mammary and salivary gland carcinomas of mice. Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind. We cloned the t(11;19) translocation that underlies the most common type of human malignant salivary gland tumor. This rearrangement fuses exon 1 from a novel gene of unknown function at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1), with exons 2-5 of a novel member of the Mastermind-like gene family (MAML2) at 11q21 (ref. 3). Similar to D. melanogaster Mastermind and MAML1 (refs. 4,5), full-length MAML2 functioned as a CSL (CBF-1, suppressor of hairless and Lag-1)-dependent transcriptional co-activator for ligand-stimulated Notch. In contrast, MECT1-MAML2 activated transcription of the Notch target gene HES1 independently of both Notch ligand and CSL binding sites. MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product. These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor. Topics: Animals; Artificial Gene Fusion; Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Mucoepidermoid; Carrier Proteins; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; DNA-Binding Proteins; Drosophila melanogaster; Drosophila Proteins; Gene Expression Regulation; Gene Rearrangement; Homeodomain Proteins; Humans; In Situ Hybridization, Fluorescence; Intercellular Signaling Peptides and Proteins; Jagged-2 Protein; Karyotyping; Ligands; Luciferases; Membrane Proteins; Molecular Sequence Data; Mutation; Neoplasms, Glandular and Epithelial; Nuclear Proteins; Promoter Regions, Genetic; Receptors, Notch; Repressor Proteins; Ribonuclease, Pancreatic; Salivary Gland Neoplasms; Signal Transduction; Trans-Activators; Transcription Factor HES-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transfection; Translocation, Genetic; Tumor Cells, Cultured	2003

Article

Year

t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma creates a novel fusion product that disrupts a Notch signaling pathway.

Nature genetics, 2003, Volume: 33, Issue:2

Truncation of Notch1 has been shown to cause a subtype of acute leukemia, and activation of Notch4 has been associated with mammary and salivary gland carcinomas of mice. Here we identify a new mechanism for disrupting Notch signaling in human tumorigenesis, characterized by altered function of a new ortholog of the Drosophila melanogaster Notch co-activator molecule Mastermind. We cloned the t(11;19) translocation that underlies the most common type of human malignant salivary gland tumor. This rearrangement fuses exon 1 from a novel gene of unknown function at 19p13, termed mucoepidermoid carcinoma translocated 1 (MECT1), with exons 2-5 of a novel member of the Mastermind-like gene family (MAML2) at 11q21 (ref. 3). Similar to D. melanogaster Mastermind and MAML1 (refs. 4,5), full-length MAML2 functioned as a CSL (CBF-1, suppressor of hairless and Lag-1)-dependent transcriptional co-activator for ligand-stimulated Notch. In contrast, MECT1-MAML2 activated transcription of the Notch target gene HES1 independently of both Notch ligand and CSL binding sites. MECT1-MAML2 induced foci formation in RK3E epithelial cells, confirming a biological effect for the fusion product. These data suggest a new mechanism to disrupt the function of a Notch co-activator in a common type of malignant salivary gland tumor.

Topics: Animals; Artificial Gene Fusion; Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Mucoepidermoid; Carrier Proteins; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; DNA-Binding Proteins; Drosophila melanogaster; Drosophila Proteins; Gene Expression Regulation; Gene Rearrangement; Homeodomain Proteins; Humans; In Situ Hybridization, Fluorescence; Intercellular Signaling Peptides and Proteins; Jagged-2 Protein; Karyotyping; Ligands; Luciferases; Membrane Proteins; Molecular Sequence Data; Mutation; Neoplasms, Glandular and Epithelial; Nuclear Proteins; Promoter Regions, Genetic; Receptors, Notch; Repressor Proteins; Ribonuclease, Pancreatic; Salivary Gland Neoplasms; Signal Transduction; Trans-Activators; Transcription Factor HES-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transfection; Translocation, Genetic; Tumor Cells, Cultured

2003