6533b838fe1ef96bd12a48ce

RESEARCH PRODUCT

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

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AbstractIt was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormonerelated peptide (PTHrP) and PTH/PTHrP receptor (PTHrPR) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrPR 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+] concentration ([Ca[2+]]) and treatment with some wellknown differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, alltrans retinoic acid and transforming growth factorβ1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrPR. 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+]] and to the addition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP. Moreover, expression of PTHrPR is also modulated by changes of [Ca[2+]] 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/PTHrPR pair in breast cancer.