Constitutive achaete-scute homologue-1 promotes airway dysplasia and lung neuroendocrine tumors in transgenic mice

The transcription factor achaete-scute homologue-1 (ASH1) is essential for neural differentiation during fetal development and is a cardinal feature of neuroendocrine (NE) tumors such as small cell lung cancer. To explore the potential of ASH1 to promote NE differentiation and tumorigenesis in the l...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-08, Vol.60 (15), p.4005-4009
Main Authors: LINNOILA, R. I, BIHONG ZHAO, DEMAYO, J. L, NELKIN, B. D, BAYLIN, S. B, DEMAYO, F. J, BALL, D. W
Format: Article
Language:English
Subjects:
Animals
Antigens, Polyomavirus Transforming - genetics
Antigens, Polyomavirus Transforming - toxicity
Basic Helix-Loop-Helix Transcription Factors
Biological and medical sciences
Bronchi - pathology
Carcinoma, Non-Small-Cell Lung - etiology
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - pathology
Cell Differentiation - physiology
Cell Division - physiology
Cocarcinogenesis
DNA-Binding Proteins - genetics
DNA-Binding Proteins - toxicity
Epithelial Cells - pathology
Female
Humans
Hyperplasia - etiology
Hyperplasia - genetics
Lung - pathology
Lung Neoplasms - etiology
Lung Neoplasms - genetics
Lung Neoplasms - pathology
Medical sciences
Metaplasia - etiology
Metaplasia - genetics
Mice
Mice, Inbred ICR
Mice, Transgenic
Neuroendocrine Tumors - etiology
Neuroendocrine Tumors - genetics
Neuroendocrine Tumors - pathology
Neurosecretory Systems - cytology
Neurosecretory Systems - physiology
Pneumology
Rabbits
Retinoblastoma Protein - physiology
Transcription Factors - genetics
Transcription Factors - toxicity
Tumor Suppressor Protein p53 - physiology
Tumors of the respiratory system and mediastinum
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Summary:The transcription factor achaete-scute homologue-1 (ASH1) is essential for neural differentiation during fetal development and is a cardinal feature of neuroendocrine (NE) tumors such as small cell lung cancer. To explore the potential of ASH1 to promote NE differentiation and tumorigenesis in the lung, we constitutively expressed the factor in nonendocrine airway epithelial cells using transgenic mice. Progressive airway hyperplasia and metaplasia developed beginning at 3 weeks of life. ASH1 potently enhanced the tumorigenic effect of SV40 large T antigen in airway epithelium. These doubly transgenic animals developed massive NE lung tumors, implying that ASH1 may cooperate with defects in p53, pRb, or related pathways in promoting NE lung carcinogenesis.
ISSN:0008-5472
1538-7445