Regulation of PTHrP and PTH/PTHrP receptor by extracellular Ca2+ concentration and hormones in the breast cancer cell line 8701-BC

It was previously reported that 8701-BC breast tumour cells express the gen e for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (P THrPR) and release immunoreactive PTHrP (iPTHrP) into the extracellular med ium. Since the regulation of PTHrP and PTHrP-R by breast cancer cells has b een poorly investigated so far, we have chosen the 8701-BC cell line as a m odel system to investigate whether alterations in the extracellular Ca2+ co ncentration ([Ca2+](e)) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, proges terone, prolactin, alltrans retinoic acid and transforming growth factor-be ta 1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect t he PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the ex pression of PTHrP-R. The data obtained indicate that 8701-BC cells are pote ntially able to utilise different start sites and mRNA splicing patterns fo r PTHrP transcription, and respond to variations of [Ca2+](e) and to the ad dition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP, Moreover, expression of PTHrP-R is also modulated by changes of [Ca2+](e) or treatment with hydrocortisone, Th is indicates that the 8701-BC cell line is a suitable in vitro model for fu rther studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.