Regulation of PTHrP and PTH/PTHrP Receptor by Extracellular Ca~(2+) Concentration and Hormones in the Breast Cancer Cell Line 8701-BC

摘要

It was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (PTHrP-R) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulaton of PTHrP and PTHrP-R by breast cancer cells has been poorly investigated so far, we have chosen the 8701-BC cell line as a model system to investigate whether alterations in the extracellular Ca~(2+) cocentration ([Ca~(2+)]_e) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, alltrans retinoic acid and transforming growth factor-β1 might(i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrP-R. The data obtained indicate that 8701-BC cells are potentially able to utilise different start sites and mRNA splicing patterns for PTHrP transcription, and respond to variations of [Ca~(2+)]_e and to the addition 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 [Ca~(2+)]_e or treatment with hydrocortisone. This indicates that the 8701-BC cell line is a suitable in vitro model for further studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.