CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, H.
Right arrow Articles by Ball, D. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, H.
Right arrow Articles by Ball, D. W.

Cell Growth & Differentiation, Vol 8, Issue 6 677-686, Copyright © 1997 by American Association of Cancer Research


ARTICLES

Tissue-specific expression of human achaete-scute homologue-1 in neuroendocrine tumors: transcriptional regulation by dual inhibitory regions

H Chen, MA Biel, MW Borges, A Thiagalingam, BD Nelkin, SB Baylin and DW Ball
Department of Surgery, Baltimore, Maryland 21231, USA.

Malignancies with neuroendocrine (NE) features such as medullary thyroid cancer (MTC) and small cell lung cancer (SCLC) are prototypic neoplasms arising from peripheral endocrine cells. The mechanisms that regulate the NE phenotype in these tumors and their cellular precursors are not well understood. However, a basic helix-loop-helix transcription factor that is homologous to Drosophila neural fate determination proteins may have a central role. Human achaete-scute homologue-1 (hASH1), a human homologue of the Drosophila achaete-scute complex, is highly expressed in MTC, SCLC, and pheochromocytomas. To determine what mechanisms allow constitutive expression of hASH1 in NE tumors, we cloned human genomic DNA fragments containing the hASH1 gene and characterized its promoter region. We show that hASH1 expression is restricted to NE cell lines by a transcriptionally regulated mechanism. Dual promoters initiate hASH1 transcription, with the predominant site being an evolutionarily conserved initiator (INR) element. Transient transfection studies provide evidence for a generalized enhancer region that has high activity in all cell lines tested. Restriction of hASH1 expression to NE tumor cells depends on two tissue-specific repressor regions, present in the proximal and distal (> 13.5 kb) 5'-flanking region. Understanding the mechanisms of tissue-specific control of hASH1 gene expression provides a useful model to explore regulatory cascades influencing both normal nervous system development and the NE phenotype of tumors such as MTC and SCLC.


This article has been cited by other articles:


Home page
Mol Cancer ResHome page
M. A. Pantaleo, M. Urbini, V. Indio, G. Ravegnini, M. Nannini, M. De Luca, G. Tarantino, S. Angelini, A. Gronchi, B. Vincenzi, et al.
Genome-Wide Analysis Identifies MEN1 and MAX Mutations and a Neuroendocrine-Like Molecular Heterogeneity in Quadruple WT GIST
Mol. Cancer Res., May 1, 2017; 15(5): 553 - 562.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
R. Jaskula-Sztul, J. Eide, S. Tesfazghi, A. Dammalapati, A. D. Harrison, X.-M. Yu, C. Scheinebeck, G. Winston-McPherson, K. R. Kupcho, M. B. Robers, et al.
Tumor-Suppressor Role of Notch3 in Medullary Thyroid Carcinoma Revealed by Genetic and Pharmacological Induction
Mol. Cancer Ther., February 1, 2015; 14(2): 499 - 512.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
M. R. Cook, S. N. Pinchot, R. Jaskula-Sztul, J. Luo, M. Kunnimalaiyaan, and H. Chen
Identification of a Novel Raf-1 Pathway Activator that Inhibits Gastrointestinal Carcinoid Cell Growth
Mol. Cancer Ther., February 1, 2010; 9(2): 429 - 437.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
L. Ning, D. Y. Greenblatt, M. Kunnimalaiyaan, and H. Chen
Suberoyl Bis-Hydroxamic Acid Activates Notch-1 Signaling and Induces Apoptosis in Medullary Thyroid Carcinoma Cells
Oncologist, February 1, 2008; 13(2): 98 - 104.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
D. Y. Greenblatt, A. M. Vaccaro, R. Jaskula-Sztul, L. Ning, M. Haymart, M. Kunnimalaiyaan, and H. Chen
Valproic Acid Activates Notch-1 Signaling and Regulates the Neuroendocrine Phenotype in Carcinoid Cancer Cells
Oncologist, August 1, 2007; 12(8): 942 - 951.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
M. Kunnimalaiyaan and H. Chen
Tumor Suppressor Role of Notch-1 Signaling in Neuroendocrine Tumors
Oncologist, May 1, 2007; 12(5): 535 - 542.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
M. Kunnimalaiyaan, A. M. Vaccaro, M. A. Ndiaye, and H. Chen
Overexpression of the NOTCH1 Intracellular Domain Inhibits Cell Proliferation and Alters the Neuroendocrine Phenotype of Medullary Thyroid Cancer Cells
J. Biol. Chem., December 29, 2006; 281(52): 39819 - 39830.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
W. F. Odenwald, W. Rasband, A. Kuzin, and T. Brody
EVOPRINTER, a multigenomic comparative tool for rapid identification of functionally important DNA
PNAS, October 11, 2005; 102(41): 14700 - 14705.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Gastrointest. Liver Physiol.Home page
M. Kunnimalaiyaan, K. Traeger, and H. Chen
Conservation of the Notch1 signaling pathway in gastrointestinal carcinoid cells
Am J Physiol Gastrointest Liver Physiol, September 13, 2005; 289(4): G636 - G642.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
A. Kazanjian, D. Wallis, N. Au, R. Nigam, K. J. T. Venken, P. T. Cagle, B. F. Dickey, H. J. Bellen, C. B. Gilks, and H. L. Grimes
Growth Factor Independence-1 Is Expressed in Primary Human Neuroendocrine Lung Carcinomas and Mediates the Differentiation of Murine Pulmonary Neuroendocrine Cells
Cancer Res., October 1, 2004; 64(19): 6874 - 6882.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
N. Pedersen, S. Mortensen, S. B. Sorensen, M. W. Pedersen, K. Rieneck, L. F. Bovin, and H. S. Poulsen
Transcriptional Gene Expression Profiling of Small Cell Lung Cancer Cells
Cancer Res., April 15, 2003; 63(8): 1943 - 1953.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
V. Sriuranpong, M. W. Borges, C. L. Strock, E. K. Nakakura, D. N. Watkins, C. M. Blaumueller, B. D. Nelkin, and D. W. Ball
Notch Signaling Induces Rapid Degradation of Achaete-Scute Homolog 1
Mol. Cell. Biol., May 1, 2002; 22(9): 3129 - 3139.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
B. A. Westerman, S. Neijenhuis, A. Poutsma, R. D. M. Steenbergen, R. H. J. Breuer, M. Egging, I. J. van Wijk, and C. B. M. Oudejans
Quantitative Reverse Transcription-Polymerase Chain Reaction Measurement of HASH1 (ASCL1), a Marker for Small Cell Lung Carcinomas with Neuroendocrine Features
Clin. Cancer Res., April 1, 2002; 8(4): 1082 - 1086.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1997 by the American Association of Cancer Research.