We studied the effect of phenytoin on the release of copeptin, the C-terminal fragment of pro-AVP, and expression of AVP gene in the human small cell lung cancer cell line Lu-165.
The aim of the study was to assess the secretion of ANP, AVP and their relative contributions to hyponatremia in SCLC patients, especially in patients with brain metastases.
We conclude that mRNA for the neuropeptides gastrin-releasing peptide and arginine vasopressin and the cholecystokinin receptor B were most SCLC-specific and RT-PCR for these markers could be used to distinguish between SCLC and NSCLC.
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.
Arginine vasopressin is detected in up to two-thirds of SCLC tumours whereas normal physiological expression is essentially restricted to the hypothalamus.
AVP release was measured by radioimmunoassay, steady state levels of AVP mRNA by solution hybridization, and AVP gene promoter activity exhibited by a 1.5 kb 5'-flanking AVP gene fragment fused to a luciferase reporter after SCLC cells were subjected to osmotic or non-osmotic conditions.
These studies demonstrate ectopic production of ANF mRNA in small cell lung cancer specimens from patients with this cancer and the syndrome of inappropriate antidiuretic hormone.