Influence of calcium and 1,25-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells.

Exposure of quiescent bovine parathyroid cells to serum or a serum substitute caused an elevation in [3H] thymidine incorporation, followed by an increase in cell number. This was preceded by a rapid transient rise in c-myc and c-fos proto-oncogene mRNA levels. Alterations in the medium calcium concentration had no effect on the growth state of quiescent parathyroid cells. In addition, varying the medium calcium concentration did not influence either the time course or the degree of induction of proto-oncogene expression or the subsequent increase in [3H] thymidine uptake or proliferation of stimulated parathyroid cells. In contrast, when 1,25-dihydroxycholecalciferol was added with serum or serum substitute to quiescent parathyroid cells, no increase in c-myc mRNA levels was observed, and the expected increase in parathyroid cell number failed to occur. The augmentation in c-fos mRNA in response to serum was not, however, altered by 1,25-dihydroxycholecalciferol. These results indicate that 1,25-dihydroxyvitamin D, but not extracellular calcium, may directly modulate parathyroid cell proliferation by altering the expression of specific replication-associated oncogenes.