Regulation of parathyroid hormone-related peptide production in normal human mammary epithelial cells in vitro.
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.
Sebag
M
M
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Henderson
J
J
Goltzman
D
D
Kremer
R
R
D001940:Breast / Q000166:cytology / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects
D006133:Growth Substances; D006728:Hormones; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D002117:Calcitriol; D006854:Hydrocortisone