This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coulson, J. M. Articles by Quinn, J. P. Search for Related Content PubMed PubMed Citation Articles by Coulson, J. M. Articles by Quinn, J. P.

Arginine Vasopressin Promoter Regulation Is Mediated by a Neuron-restrictive Silencer Element in Small Cell Lung Cancer¹

CRC Academic Unit of Clinical Oncology, University of Nottingham, City Hospital, Nottingham NG5 1PB [J. M. C., P. J. W.], and Veterinary Pathology, University of Edinburgh, Edinburgh EH9 1QH [C. E. F., J. P. Q.], United Kingdom

Arginine vasopressin (AVP) is often expressed in small cell lung cancer (SCLC), and a 65-bp AVP minimal promoter fragment is sufficient to restrict activity to SCLC in vitro. We now describe a motif with homology to the neuron-restrictive silencer element (NRSE) within this fragment. Electrophoretic mobility shift analysis demonstrated that multiple specific complexes are bound by this motif. These complexes are cross-competed with a characterized SCG10 NRSE probe and do not bind to the AVP probe with a specific mutation in the NRSE. The complexes vary in mobility between lung tumor cell lines, showing different levels of AVP expression, and some are differentially bound in SCLC. Overexpression of a neuron-restrictive silencer factor expression construct can silence reporter gene expression supported by the AVP promoter in SCLC, although this was dependent on both the level of endogenous AVP expression in the cells and putative enhancer elements in larger promoter constructs. Activation of the proximal AVP promoter in SCLC is therefore proposed to, at least partially, rely on modulation of normal repressor activity at the NRSE.

This article has been cited by other articles:

				J. M. Coulson, J. L. Edgson, P. J. Woll, and J. P. Quinn A Splice Variant of the Neuron-restrictive Silencer Factor Repressor Is Expressed in Small Cell Lung Cancer: A Potential Role in Derepression of Neuroendocrine Genes and a Useful Clinical Marker Cancer Res., April 1, 2000; 60(7): 1840 - 1844. [Abstract] [Full Text]