Arginine vasopressin promoter regulation is mediated by a neuron-restrictive silencer element in small cell lung cancer

Arginine vasopressin (AVP) is often expressed in small cell Lung cancer (SC LC), and a 65-bp AVP minimal promoter fragment is sufficient to restrict ac tivity to SCLC in vitro, We now describe a motif with homology to the neuro n-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 characterize d SCG10 NRSE probe and do not bind to the AVP probe with a specific mutatio n in the NRSE. The complexes vary in mobility between lung tumor cell Lines , showing different levels of AVP expression, and some are differentially b ound in SCLC. Overexpression of a neuron-restrictive silencer factor expres sion construct can silence reporter gene expression supported by the AVP pr omoter in SCLC, although this was dependent on both the Level of endogenous AVP expression in the cells and putative enhancer elements in larger promo ter constructs. Activation of the proximal AVP promoter in SCLC is therefor e proposed to, at least partially, rely on modulation of normal repressor a ctivity at the NRSE.