Glucocorticoid receptor-mediated expression of kallikrein 10 in human breast cancer cell lines.
Using the breast cell lines MCF-10A, MDA-MB-468 and T-47D, we investigated the role of various glucocorticoids in regulating human kallikrein 10 expression. We found that increased concentrations of glucocorticoids decreased KLK10 expression in MCF-10A and increased KLK10 expression in MDA-MB-468 and T-47D cells. Stimulation of the cell lines using other steroid hormones did not yield any difference in KLK10 expression in MCF-10A and MDA-MB-468 cells, suggesting that regulation of KLK10 occurs primarily through glucocorticoids. However, T-47D cells expressed higher levels of KLK10 upon dihydrotestosterone stimulation. Blocking the glucocorticoid receptor (GR) demonstrated that the mechanisms of induction and repression are different in the three cell lines studied. Taken together, our results suggest an alternative mode of KLK10 regulation - by glucocorticoids via GR-dependent mechanisms.
Kulasingam
Vathany
V
Department of Laboratory Medicine and Pathobiology, University of Toronto, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto M5G 1X5, ON, Canada.
Diamandis
Eleftherios P
EP
D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; C100936:KLK10 protein, human; D007610:Kallikreins