AJP - Cell Physiology, Vol 267, Issue 3 C723-C730, Copyright © 1994 by American Physiological Society

ARTICLES

Regulation of parathyroid hormone-related peptide production in normal human mammary epithelial cells in vitro

M. Sebag, J. Henderson, D. Goltzman and R. Kremer
Department of Medicine, McGill University, Montreal, Quebec, Canada.

We have examined the expression and production of parathyroid hormone-related peptide (PTHRP) in primary cultures of normal human mammary epithelial cells (HMEC) derived from nonlactating breast tissue. In response to growth factors such as insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor (EGF), immunoreactive PTHRP was released into conditioned medium, and PTHRP mRNA rapidly increased. In contrast, hydrocortisone and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibited these effects in a dose-dependent manner. Addition of prolactin (PRL) in the presence or absence of insulin, IGF-I, or EGF did not influence PTHRP production during the time course studied. To investigate whether these factors were acting at the transcriptional level, we performed nuclear run-on assays and demonstrated that IGF-I increased PTHRP gene transcription whereas hydrocortisone and 1,25(OH)2D3 inhibited this effect. These studies therefore demonstrate that IGF-I, EGF, 1,25(OH)2D3, and hydrocortisone modulate PTHRP expression in HMEC and that these effects occur in part at the level of gene transcription. Additionally, PRL, a known stimulator of PTHRP expression in vivo, has no effect in this in vitro model.

This article has been cited by other articles:

				K. El Abdaimi, V. Papavasiliou, D. Goltzman, and R. Kremer Expression and regulation of parathyroid hormone-related peptide in normal and malignant melanocytes Am J Physiol Cell Physiol, October 1, 2000; 279(4): C1230 - C1238. [Abstract] [Full Text] [PDF]