Hormone receptors and cyclic nucleotide metabolism in cancer cells.
The possibility of a relationship between cyclic AMP formation and metabolic processes in tumours has been investigated. Changes in basal activity and hormone-responsiveness of adenylate cyclase were demonstrated in plasma membranes and intact cells from pre-cancerous liver of rats fed a diet containing the carcinogen 3'-methyl-4-dimethylaminoazobenzene. Basal adenylate cyclase activity in hyperplastic parathyroid gland membranes was 200% higher than that in parathyroid adenoma membranes, corresponding with their relative rates of parathyroid hormone secretion in vitro. Membrane adenylate cyclase activity in hypernephromas was consistently 100--300% higher than in adjacent human renal cortex. Furthermore the adenylate cyclase activity of the tumour membranes was not influenced by a wide range of hormones which were effective stimulants in 'normal' renal cortex membranes. Conversion of 25-hydroxycholecalciferol to 1,25-dihydrocholecalciferol could not be demonstrated in either hypernephroma or adjacent renal cortical tissue. However, three of the four hypernephromas tested secreted a bone-resorbing factor. Cyclic AMP formation was increased by salmon, human and porcine calcitonins in both plasma membranes and intact cells from a poorly differentiated epidermoid cell carcinoma which was itself secreting calcitonin in culture. This phenomenon might be related to a feedback regulation of calcitonin production in this cell line. The observations are consistent with the concept of a relationship between cyclic AMP formation and certain metabolic functions (e.g. hormone production) in tumour cells.