Parathyroid hormone-related protein increases cAMP production in mammary epithelial cells.

Parathyroid hormone-related protein (PTHrP) is a major cause of malignant hypercalcemia but has been found in many nontumoral tissues as well. Thus it is produced by the mammary gland during lactation and released into milk. Whether PTHrP directly affects breast tissue is however not known. We investigated the effects of PTHrP on adenosine 3',5'-cyclic monophosphate (cAMP) production in primary cultures of mammary epithelial cells isolated from lactating rats. On the 7th day in culture, synthetic PTHrP-(1-34), recombinant (r) PTHrP-(1-108), and rPTHrP-(1-141) stimulated cAMP production in a concentration-dependent manner. Thus PTHrP-(1-34) induced a 1.92 +/- 0.04-fold stimulation of cAMP production (mean +/- SE, n = 5 separate experiments, P < 0.001). At the time of maximal responsiveness to PTHrP, a significant proportion of the cells was characterized by an elongated shape and a positive immunofluorescent staining for both prekeratin and alpha-smooth muscle actin 1, compatible with a myoepithelial phenotype. It therefore appears that PTHrP can stimulate the production of cAMP in mammary cells, suggesting a possible autocrine/paracrine regulatory function for PTHrP in breast tissue.

[1]  R. Offringa,et al.  Regulation of parathyroid hormonelike protein production in cultured normal and malignant keratinocytes. , 1992, The Journal of investigative dermatology.

[2]  R. Rizzoli,et al.  Parathyroid hormone‐related protein production by primary cultures of mammary epithelial cells , 1992, Journal of cellular physiology.

[3]  L. Duong,et al.  Concentrations of parathyroid hormone-related protein in rat milk change with duration of lactation and interval from previous suckling, but not with milk calcium. , 1992, Endocrinology.

[4]  J. Britto,et al.  A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts. , 1991, Endocrinology.

[5]  A. F. Stewart,et al.  Immunoaffinity purification of parathyroid hormone‐related protein from bovine milk and human keratinocyte‐conditioned medium , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  D. Banville,et al.  Regulation of parathyroid hormone-like peptide in cultured normal human keratinocytes. Effect of growth factors and 1,25 dihydroxyvitamin D3 on gene expression and secretion. , 1991, The Journal of clinical investigation.

[7]  J. Ratcliffe,et al.  Identification and partial characterization of parathyroid hormone-related protein in human and bovine milk. , 1990, The Journal of endocrinology.

[8]  A. Broadus,et al.  Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[9]  H. Gharib,et al.  Parathyroid hormone-related protein and hypercalcemia secondary to massive mammary hyperplasia. , 1990 .

[10]  S. Eber,et al.  Purification and properties of parathyroid hormone-related peptide isolated from milk. , 1990, Endocrinology.

[11]  D. Banville,et al.  Parathyroid hormone-like peptide: Molecular characterization and biological properties , 1989, Trends in Endocrinology & Metabolism.

[12]  D. Diep,et al.  High levels of a parathyroid hormone-like protein in milk. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Hayman,et al.  Parathyroid hormone‐related protein: Immunohistochemical localization in cancers and in normal skin , 1989, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  E. Brown,et al.  Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. , 1988, Molecular endocrinology.

[15]  G. Rodan,et al.  Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. , 1988, Science.

[16]  G. Gabbiani,et al.  A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation , 1986, The Journal of cell biology.

[17]  P. Rudland,et al.  Characterization of rat mammary cell types in primary culture: lectins and antisera to basement membrane and intermediate filament proteins as indicators of cellular heterogeneity. , 1985, Journal of cell science.

[18]  J. Saurat,et al.  The intermediate filament proteins of rabbit normal epidermal Merkel cells are cytokeratins. , 1984, The Journal of investigative dermatology.

[19]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[20]  T. Martin,et al.  Parathyroid hormone-related protein in milk and its correlation with bovine milk calcium. , 1991, The Journal of endocrinology.

[21]  T. Martin,et al.  Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action. , 1989, Recent progress in hormone research.