Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: interactions between glucocorticoids and second messengers

Mol Endocrinol. 1991 Jun;5(6):795-801. doi: 10.1210/mend-5-6-795.

Abstract

The role of glucocorticoids and second messenger systems in the regulation of the vasopressin (VP) gene was studied in the human small cell lung carcinoma cell line GLC-8. Small cell lung carcinoma GLC-8 cells express VP mRNA and contain both glucocorticoid and mineralocorticoid receptors. Treatment with the synthetic glucocorticoid dexamethasone when added alone at 10(-8) M had no effect on the VP mRNA level and decreased the level by 30% at 10(-6) M. However, the effect of dexamethasone changed to positive when cells were simultaneously treated with cAMP-enhancing agents. VP mRNA levels, which were elevated by 1.5- to 2-fold by the cAMP-enhancing agents alone, increased a further 1.5- to 3-fold by dexamethasone. Thus, the combined effect of dexamethasone and cAMP stimulation was a 3- to 7.5-fold increase in VP mRNA levels. Long term treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reduced the VP mRNA level by 75%. The TPA-suppressed VP mRNA levels could be up-regulated about 6-fold by simultaneous treatment with 8-bromo-cAMP. Dexamethasone did not alter the TPA-suppressed VP mRNA levels. These results indicate that both cAMP and protein kinase-C pathways as well as glucocorticoid receptors are involved in the regulation of VP mRNA levels and that these factors interact. This leads to a negative or positive response of VP gene expression to glucocorticoids in a state-dependent manner. The interactions may be of significance in a physiological context and relate to the different regulation of VP-expressing systems in the brain.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology*
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology*
  • Aldosterone / metabolism
  • Carcinoma, Small Cell / genetics*
  • Cell Line
  • Cyclic AMP / physiology*
  • Dexamethasone / metabolism
  • Dexamethasone / pharmacology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hydrocortisone / metabolism
  • Lung Neoplasms / genetics*
  • RNA, Messenger / genetics*
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Glucocorticoid / physiology*
  • Second Messenger Systems* / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic / drug effects*
  • Vasopressins / genetics*

Substances

  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Vasopressins
  • 8-Bromo Cyclic Adenosine Monophosphate
  • Aldosterone
  • Dexamethasone
  • Cyclic AMP
  • Tetradecanoylphorbol Acetate
  • 1-Methyl-3-isobutylxanthine
  • Hydrocortisone