BIOMAT Database Logo BIOMAT Database Logo

Basic helix-loop-helix transcription factor profiling of lung tumors shows aberrant expression of the proneural gene atonal homolog 1 (ATOH1, HATH1, MATH1) in neuroendocrine tumors. 2007

B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.

Microarray-based expression profiling studies of lung adenocarcinomas have defined neuroendocrine subclasses with poor prognosis. As neuroendocrine development is regulated by members of the achaete-scute and atonal classes of basic helix-loop-helix (bHLH) transcription factors, we analyzed lung tumors for expression of these factors. Out of 13 bHLH genes tested, 4 genes, i.e., achaete-scute complex-like 1 (ASCL1, HASH1, Mash1), atonal homolog 1 (ATOH1, HATH1, MATH1), NEUROD4 (ATH-3, Atoh3, MATH-3) and neurogenic differentiation factor 1 (NEUROD1, NEUROD, BETA2), showed differential expression among lung tumors and absent or low expression in normal lung. As expected, tumors that have high levels of ASCL1 also express neuroendocrine markers, and we found that this is accompanied by increased levels of NEUROD1. In addition, we found ATOH1 expression in 9 (16%) out of 56 analyzed adenocarcinomas and these tumors showed neuroendocrine features as shown by dopa decarboxylase mRNA expression and immunostaining for neuroendocrine markers. ATOH1 expression as well as NEUROD4 was observed in small cell lung carcinoma (SCLC), a known neuroendocrine tumor. Since ATOH1 is not known to be involved in normal lung development, our results suggest that aberrant activation of ATOH1 leads to a neuroendocrine phenotype similar to what is observed for ASCL1 activation during normal neuroendocrine development and in lung malignancies. Our preliminary data indicate that patients with ATOH1-expressing adenocarcinomas might have a worse prognosis.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012334 RNA, Neoplasm RNA present in neoplastic tissue. Neoplasm RNA
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D016019 Survival Analysis A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. Analysis, Survival,Analyses, Survival,Survival Analyses
D051792 Basic Helix-Loop-Helix Transcription Factors A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF. Basic Helix-Loop-Helix Transcription Factor,bHLH Protein,bHLH Transcription Factor,bHLH Proteins,bHLH Transcription Factors,Basic Helix Loop Helix Transcription Factor,Basic Helix Loop Helix Transcription Factors,Factor, bHLH Transcription,Protein, bHLH,Transcription Factor, bHLH,Transcription Factors, bHLH
D017931 DNA Primers Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques. DNA Primer,Oligodeoxyribonucleotide Primer,Oligodeoxyribonucleotide Primers,Oligonucleotide Primer,Oligonucleotide Primers,Primer, DNA,Primer, Oligodeoxyribonucleotide,Primer, Oligonucleotide,Primers, DNA,Primers, Oligodeoxyribonucleotide,Primers, Oligonucleotide

Related Publications

B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
The intestine-specific homeobox gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math1.
July 2006, Differentiation; research in biological diversity,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Significance of proneural basic helix-loop-helix transcription factors in neuroendocrine differentiation of fetal lung epithelial cells and lung carcinoma cells.
January 2001, Histology and histopathology,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Developmental and evolutionary aspects of the basic helix-loop-helix transcription factors Atonal-like 1 and Achaete-scute homolog 2 in the jellyfish.
May 2004, Developmental biology,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Expression of the neurogenic basic helix-loop-helix transcription factor NEUROG1 identifies a subgroup of medulloblastomas not expressing ATOH1.
July 2007, Neuro-oncology,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Targeted disruption of NeuroD, a proneural basic helix-loop-helix factor, impairs distal lung formation and neuroendocrine morphology in the neonatal lung.
July 2008, The Journal of biological chemistry,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Function of pioneer neurons specified by the basic helix-loop-helix transcription factor atonal in neural development.
September 2016, Neural regeneration research,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Conversion of ectoderm into a neural fate by ATH-3, a vertebrate basic helix-loop-helix gene homologous to Drosophila proneural gene atonal.
January 1997, The EMBO journal,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Basic helix-loop-helix transcription factor gene family phylogenetics and nomenclature.
July 2010, Differentiation; research in biological diversity,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration.
January 2008, The Journal of neuroscience : the official journal of the Society for Neuroscience,
B A Westerman, and R H J Breuer, and A Poutsma, and A Chhatta, and L A Noorduyn, and M G J Koolen, and P E Postmus, and M A Blankenstein, and C B M Oudejans
Embryonic expression of mSharp-1/mDEC2, which encodes a basic helix-loop-helix transcription factor.
June 2002, Mechanisms of development,
Copied contents to your clipboard!