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British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Jul;72(1):90–95. doi: 10.1038/bjc.1995.282

Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor expression and mitogenic responses in human breast cancer cell lines.

M A Birch 1, J A Carron 1, M Scott 1, W D Fraser 1, J A Gallagher 1
PMCID: PMC2034135  PMID: 7599071

Abstract

Previous reports have shown the production of parathyroid hormone-related protein (PTHrP) by breast cancer cells in vivo and in vitro. We have investigated the expression of the PTH/PTHrP receptor by the human breast cancer cell lines MCF-7, ZR-75-1, T-47-D, SK-BR-3, Hs578T and MDA-MB231. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis, we detected transcripts for the receptor in MCF-7, SK-BR-3 and MDA-MB231 cells. There was no evidence of receptor mRNA in ZR-75-1 and Hs578T cells. Furthermore, Northern blot analysis of mRNA from MCF-7 cells showed two transcripts of 1.5 and 2.4 kb which coded for the PTH/PTHrP receptor. Expression of PTH/PTHrP receptor mRNA by the breast cancer cell lines was also correlated with the detection of PTHrP transcripts. RT-PCR demonstrated PTHrP mRNA in MCF-7, ZR-75-1, T-47-D and Hs578T cells, but not in SK-BR-3 and MDA-MB231 cells. The detection of receptor transcripts was complemented by [3H]thymidine and bromodeoxyuridine incorporation studies, in which mitogenic responses to PTH and PTHrP were observed in MCF-7 cells but not in Hs578T cells. In response to both PTH(1-34) and PTHrP(1-34), quiescent MCF-7 cells proliferated in a similar dose-dependent manner (1.6-100 ng ml-1). No mitogenic effects of these peptides were observed with Hs578T cells. In addition, levels of intracellular cAMP were measured in MCF-7 and Hs578T cells in response to PTHrP(1-34). In MCF-7 cells there was a significant rise in cAMP with 100 ng ml-1 PTHrP(1-34). The expression of PTH/PTHrP receptor by breast cancer cells suggests that PTHrP may be a paracrine/autocrine regulator of breast carcinoma.

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  1. Abou-Samra A. B., Jüppner H., Force T., Freeman M. W., Kong X. F., Schipani E., Urena P., Richards J., Bonventre J. V., Potts J. T., Jr Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular free calcium. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2732–2736. doi: 10.1073/pnas.89.7.2732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benítez-Verguizas J., Esbrit P. Proliferative effect of parathyroid hormone-related protein on the hypercalcemic Walker 256 carcinoma cell line. Biochem Biophys Res Commun. 1994 Feb 15;198(3):1281–1289. doi: 10.1006/bbrc.1994.1181. [DOI] [PubMed] [Google Scholar]
  3. Bouizar Z., Spyratos F., Deytieux S., de Vernejoul M. C., Jullienne A. Polymerase chain reaction analysis of parathyroid hormone-related protein gene expression in breast cancer patients and occurrence of bone metastases. Cancer Res. 1993 Nov 1;53(21):5076–5078. [PubMed] [Google Scholar]
  4. Broadus A. E., Mangin M., Ikeda K., Insogna K. L., Weir E. C., Burtis W. J., Stewart A. F. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med. 1988 Sep 1;319(9):556–563. doi: 10.1056/NEJM198809013190906. [DOI] [PubMed] [Google Scholar]
  5. Bundred N. J., Ratcliffe W. A., Walker R. A., Coley S., Morrison J. M., Ratcliffe J. G. Parathyroid hormone related protein and hypercalcaemia in breast cancer. BMJ. 1991 Dec 14;303(6816):1506–1509. doi: 10.1136/bmj.303.6816.1506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burtis W. J., Wu T., Bunch C., Wysolmerski J. J., Insogna K. L., Weir E. C., Broadus A. E., Stewart A. F. Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy. J Biol Chem. 1987 May 25;262(15):7151–7156. [PubMed] [Google Scholar]
  7. Burton P. B., Moniz C., Knight D. E. Parathyroid hormone related peptide can function as an autocrine growth factor in human renal cell carcinoma. Biochem Biophys Res Commun. 1990 Mar 30;167(3):1134–1138. doi: 10.1016/0006-291x(90)90641-y. [DOI] [PubMed] [Google Scholar]
  8. Chase L. R., Fedak S. A., Aurbach G. D. Activation of skeletal adenyl cyclase by parathyroid hormone in vitro. Endocrinology. 1969 Apr;84(4):761–768. doi: 10.1210/endo-84-4-761. [DOI] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Cosman F., Morrow B., Kopal M., Bilezikian J. P. Stimulation of inositol phosphate formation in ROS 17/2.8 cell membranes by guanine nucleotide, calcium, and parathyroid hormone. J Bone Miner Res. 1989 Jun;4(3):413–420. doi: 10.1002/jbmr.5650040317. [DOI] [PubMed] [Google Scholar]
  11. Donahue H. J., Fryer M. J., Eriksen E. F., Heath H., 3rd Differential effects of parathyroid hormone and its analogues on cytosolic calcium ion and cAMP levels in cultured rat osteoblast-like cells. J Biol Chem. 1988 Sep 25;263(27):13522–13527. [PubMed] [Google Scholar]
  12. Evely R. S., Bonomo A., Schneider H. G., Moseley J. M., Gallagher J., Martin T. J. Structural requirements for the action of parathyroid hormone-related protein (PTHrP) on bone resorption by isolated osteoclasts. J Bone Miner Res. 1991 Jan;6(1):85–93. doi: 10.1002/jbmr.5650060114. [DOI] [PubMed] [Google Scholar]
  13. Farr H. W., Fahey T. J., Jr, Nash A. G., Farr C. M. Primary hyperparathyroidism and cancer. Am J Surg. 1973 Oct;126(4):539–543. doi: 10.1016/s0002-9610(73)80046-7. [DOI] [PubMed] [Google Scholar]
  14. Ferrari S. L., Rizzoli R., Bonjour J. P. Parathyroid hormone-related protein production by primary cultures of mammary epithelial cells. J Cell Physiol. 1992 Feb;150(2):304–311. doi: 10.1002/jcp.1041500213. [DOI] [PubMed] [Google Scholar]
  15. Francini G., Maioli E., Petrioli R., Paffetti P., Gonnelli S., Aquino A. Production of parathyroid hormone and parathyroid-hormone-related protein by breast cancer cells in culture. J Cancer Res Clin Oncol. 1993;119(7):421–425. doi: 10.1007/BF01218424. [DOI] [PubMed] [Google Scholar]
  16. Hamilton J. A., Lingelbach S., Partridge N. C., Martin T. J. Regulation of plasminogen activator production by bone-resorbing hormones in normal and malignant osteoblasts. Endocrinology. 1985 Jun;116(6):2186–2191. doi: 10.1210/endo-116-6-2186. [DOI] [PubMed] [Google Scholar]
  17. Horiuchi N., Caulfield M. P., Fisher J. E., Goldman M. E., McKee R. L., Reagan J. E., Levy J. J., Nutt R. F., Rodan S. B., Schofield T. L. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro. Science. 1987 Dec 11;238(4833):1566–1568. doi: 10.1126/science.3685994. [DOI] [PubMed] [Google Scholar]
  18. Luparello C., Ginty A. F., Gallagher J. A., Pucci-Minafra I., Minafra S. Transforming growth factor-beta 1, beta 2, and beta 3, urokinase and parathyroid hormone-related peptide expression in 8701-BC breast cancer cells and clones. Differentiation. 1993 Dec;55(1):73–80. doi: 10.1111/j.1432-0436.1993.tb00034.x. [DOI] [PubMed] [Google Scholar]
  19. MacDonald B. R., Gallagher J. A., Russell R. G. Parathyroid hormone stimulates the proliferation of cells derived from human bone. Endocrinology. 1986 Jun;118(6):2445–2449. doi: 10.1210/endo-118-6-2445. [DOI] [PubMed] [Google Scholar]
  20. Martin T. J., Suva L. J. Parathyroid hormone-related protein in hypercalcaemia of malignancy. Clin Endocrinol (Oxf) 1989 Nov;31(5):631–647. doi: 10.1111/j.1365-2265.1989.tb01288.x. [DOI] [PubMed] [Google Scholar]
  21. Moniz C., Burton P. B., Malik A. N., Dixit M., Banga J. P., Nicolaides K., Quirke P., Knight D. E., McGregor A. M. Parathyroid hormone-related peptide in normal human fetal development. J Mol Endocrinol. 1990 Dec;5(3):259–266. doi: 10.1677/jme.0.0050259. [DOI] [PubMed] [Google Scholar]
  22. Moseley J. M., Kubota M., Diefenbach-Jagger H., Wettenhall R. E., Kemp B. E., Suva L. J., Rodda C. P., Ebeling P. R., Hudson P. J., Zajac J. D. Parathyroid hormone-related protein purified from a human lung cancer cell line. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5048–5052. doi: 10.1073/pnas.84.14.5048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Okano K., Wu S., Huang X., Pirola C. J., Juppner H., Abou-Samra A. B., Segre G. V., Iwasaki K., Fagin J. A., Clemens T. L. Parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptor and its messenger ribonucleic acid in rat aortic vascular smooth muscle cells and UMR osteoblast-like cells: cell-specific regulation by angiotensin-II and PTHrP. Endocrinology. 1994 Sep;135(3):1093–1099. doi: 10.1210/endo.135.3.8070351. [DOI] [PubMed] [Google Scholar]
  24. Powell G. J., Southby J., Danks J. A., Stillwell R. G., Hayman J. A., Henderson M. A., Bennett R. C., Martin T. J. Localization of parathyroid hormone-related protein in breast cancer metastases: increased incidence in bone compared with other sites. Cancer Res. 1991 Jun 1;51(11):3059–3061. [PubMed] [Google Scholar]
  25. Schöfl C., Cuthbertson K. S., Gallagher J. A., Pennington S. R., Cobbold P. H., Brabant G., Hesch R. D., von zur Mühlen A. Measurement of intracellular Ca2+ in single aequorin-injected and suspensions of fura-2-loaded ROS 17/2.8 cells and normal human osteoblasts. Effect of parathyroid hormone. Biochem J. 1991 Feb 15;274(Pt 1):15–20. doi: 10.1042/bj2740015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Southby J., Kissin M. W., Danks J. A., Hayman J. A., Moseley J. M., Henderson M. A., Bennett R. C., Martin T. J. Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer. Cancer Res. 1990 Dec 1;50(23):7710–7716. [PubMed] [Google Scholar]
  27. Stewart A. F., Wu T., Goumas D., Burtis W. J., Broadus A. E. N-terminal amino acid sequence of two novel tumor-derived adenylate cyclase-stimulating proteins: identification of parathyroid hormone-like and parathyroid hormone-unlike domains. Biochem Biophys Res Commun. 1987 Jul 31;146(2):672–678. doi: 10.1016/0006-291x(87)90581-x. [DOI] [PubMed] [Google Scholar]
  28. Strewler G. J., Stern P. H., Jacobs J. W., Eveloff J., Klein R. F., Leung S. C., Rosenblatt M., Nissenson R. A. Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. J Clin Invest. 1987 Dec;80(6):1803–1807. doi: 10.1172/JCI113275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thiede M. A., Rodan G. A. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science. 1988 Oct 14;242(4876):278–280. doi: 10.1126/science.3175653. [DOI] [PubMed] [Google Scholar]
  30. Ureña P., Kong X. F., Abou-Samra A. B., Jüppner H., Kronenberg H. M., Potts J. T., Jr, Segre G. V. Parathyroid hormone (PTH)/PTH-related peptide receptor messenger ribonucleic acids are widely distributed in rat tissues. Endocrinology. 1993 Aug;133(2):617–623. doi: 10.1210/endo.133.2.8393771. [DOI] [PubMed] [Google Scholar]
  31. Vargas S. J., Gillespie M. T., Powell G. J., Southby J., Danks J. A., Moseley J. M., Martin T. J. Localization of parathyroid hormone-related protein mRNA expression in breast cancer and metastatic lesions by in situ hybridization. J Bone Miner Res. 1992 Aug;7(8):971–979. doi: 10.1002/jbmr.5650070814. [DOI] [PubMed] [Google Scholar]
  32. Walsh C. A., Birch M. A., Fraser W. D., Robinson J., Lawton R., Dorgan J., Klenerman L., Gallagher J. A. Primary cultures of human bone-derived cells produce parathyroid hormone-related protein: a study of 40 patients of varying age and pathology. Bone Miner. 1994 Oct;27(1):43–50. doi: 10.1016/s0169-6009(08)80185-7. [DOI] [PubMed] [Google Scholar]

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