title: Induction of calcitonin receptor expression by glucocorticoids in T47D human breast cancer cells.
abstract: When T47D cells were maintained long term in medium containing 0.1 mumol cortisol/l, calcitonin receptor (CTR) expression was stimulated compared with the very low levels of binding in untreated cells grown from frozen stocks. The time-course of the appearance of CTR following treatment with cortisol was slow, requiring up to 3 weeks of continuous exposure of the cells to the steroid. Binding capacity of control cells also increased slowly with time in culture, but after 3 months was only 20-30% of that in cells continuously treated with cortisol. Removal of cortisol resulted in rapid loss of CTR so that binding was reduced to approximately 50% of treated cell levels within 1 week of removal. Scatchard analysis of the binding data showed that the increased binding capacity induced by cortisol was due solely to a change in average receptor number per cell, with no change in receptor affinity. That this induction of CTR was due to a glucocorticoid effect was shown by the more rapid (less than 96 h) and more potent (less than 1 nmol/l) action of dexamethasone than of cortisol. In addition, induction was inhibited by the glucocorticoid inhibitor RU486. The induced receptors were shown to be functional, since salmon calcitonin-stimulated adenylate cyclase was induced in parallel with CTR. These results indicate that glucocorticoids are potential regulators of the CTR.
authors.affiliation: St Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: V P
authors.initials: VP
authors.lastname: Michelangeli
authors.forename: D M
authors.initials: DM
authors.lastname: Findlay
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002116:Calcitonin / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D015735:Mifepristone / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D018003:Receptors, Calcitonin; D011956:Receptors, Cell Surface; D015735:Mifepristone; D003907:Dexamethasone; D002116:Calcitonin; D000242:Cyclic AMP; D006854:Hydrocortisone