Abstract
Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified aminoterminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism.
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- Campos R. V., Asa S. L., Drucker D. J. Immunocytochemical localization of parathyroid hormone-like peptide in the rat fetus. Cancer Res. 1991 Dec 1;51(23 Pt 1):6351–6357. [PubMed] [Google Scholar]
- 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]
- Gupta A., Martin K. J., Miyauchi A., Hruska K. A. Regulation of cytosolic calcium by parathyroid hormone and oscillations of cytosolic calcium in fibroblasts from normal and pseudohypoparathyroid patients. Endocrinology. 1991 Jun;128(6):2825–2836. doi: 10.1210/endo-128-6-2825. [DOI] [PubMed] [Google Scholar]
- Hellman P., Ridefelt P., Juhlin C., Akerström G., Rastad J., Gylfe E. Parathyroid-like regulation of parathyroid-hormone-related protein release and cytoplasmic calcium in cytotrophoblast cells of human placenta. Arch Biochem Biophys. 1992 Feb 14;293(1):174–180. doi: 10.1016/0003-9861(92)90381-6. [DOI] [PubMed] [Google Scholar]
- Henderson J. E., Kremer R., Rhim J. S., Goltzman D. Identification and functional characterization of adenylate cyclase-linked receptors for parathyroid hormone-like peptides on immortalized human keratinocytes. Endocrinology. 1992 Jan;130(1):449–457. doi: 10.1210/endo.130.1.1309343. [DOI] [PubMed] [Google Scholar]
- Khosla S., van Heerden J. A., Gharib H., Jackson I. T., Danks J., Hayman J. A., Martin T. J. Parathyroid hormone-related protein and hypercalcemia secondary to massive mammary hyperplasia. N Engl J Med. 1990 Apr 19;322(16):1157–1157. doi: 10.1056/NEJM199004193221613. [DOI] [PubMed] [Google Scholar]
- Koehl R. H., Snyder R. E., Hutter R. V., Foote F. W., Jr The incidence and significance of calcifications within operative breast specimens. Am J Clin Pathol. 1970 Jan;53(1):3–14. doi: 10.1093/ajcp/53.1.3. [DOI] [PubMed] [Google Scholar]
- Law F. M., Moate P. J., Leaver D. D., Diefenbach-Jagger H., Grill V., Ho P. W., Martin T. J. Parathyroid hormone-related protein in milk and its correlation with bovine milk calcium. J Endocrinol. 1991 Jan;128(1):21–26. doi: 10.1677/joe.0.1280021. [DOI] [PubMed] [Google Scholar]
- Lepre F., Grill V., Ho P. W., Martin T. J. Hypercalcemia in pregnancy and lactation associated with parathyroid hormone-related protein. N Engl J Med. 1993 Mar 4;328(9):666–667. doi: 10.1056/NEJM199303043280917. [DOI] [PubMed] [Google Scholar]
- McGrath C. M., Soule H. D. Calcium regulation of normal human mammary epithelial cell growth in culture. In Vitro. 1984 Aug;20(8):652–662. doi: 10.1007/BF02619616. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Ralston S. H., Danks J., Hayman J., Fraser W. D., Stewart C. S., Martin T. J. Parathyroid hormone-related protein of malignancy: immunohistochemical and biochemical studies in normocalcaemic and hypercalcaemic patients with cancer. J Clin Pathol. 1991 Jun;44(6):472–476. doi: 10.1136/jcp.44.6.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Russo J., Frederick J., Ownby H. E., Fine G., Hussain M., Krickstein H. I., Robbins T. O., Rosenberg B. Predictors of recurrence and survival of patients with breast cancer. Am J Clin Pathol. 1987 Aug;88(2):123–131. doi: 10.1093/ajcp/88.2.123. [DOI] [PubMed] [Google Scholar]
- Soifer N. E., Dee K. E., Insogna K. L., Burtis W. J., Matovcik L. M., Wu T. L., Milstone L. M., Broadus A. E., Philbrick W. M., Stewart A. F. Parathyroid hormone-related protein. Evidence for secretion of a novel mid-region fragment by three different cell types. J Biol Chem. 1992 Sep 5;267(25):18236–18243. [PubMed] [Google Scholar]
- 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]
- Suva L. J., Winslow G. A., Wettenhall R. E., Hammonds R. G., Moseley J. M., Diefenbach-Jagger H., Rodda C. P., Kemp B. E., Rodriguez H., Chen E. Y. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science. 1987 Aug 21;237(4817):893–896. doi: 10.1126/science.3616618. [DOI] [PubMed] [Google Scholar]
- 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]



