| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine and 2 Division of Surgical Neurology, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; and 3 Department of Neurosurgery, University of Kocaeli Medical School, Kocaeli, Turkey
Parathyroid hormone-related protein (PTHrP) is the major mediator of the humoral hypercalcemia of malignancy and of malignant osteolysis associated with skeletal metastases of common epithelial cancers. PTHrP secretion is regulated by the extracellular calcium concentration ([Ca2+]o) in several types of normal and malignant cells. Because the [Ca2+]o-sensing receptor (CaR) is a key mediator of [Ca2+]o-regulated hormone secretion [e.g., of parathyroid hormone (PTH) by parathyroid chief cells], we investigated the expression of the CaR and PTHrP in normal and neoplastic glial cells and studied the effects of [Ca2+]o on PTHrP secretion. Our results show that primary embryonic human astrocytes (HPA) express CaR mRNA and protein as detected by RT-PCR and Western analysis, respectively. Furthermore, astrocytomas and meningiomas also express the CaR at similar levels as assessed by RT-PCR and Northern and Western blot analyses. HPA and astrocytomas express transcripts encoding all three known isoforms of PTHrP [PTHrP(139), PTHrP(141), and PTHrP(173), comprising 139, 141, and 173 predicted amino acid residues, respectively] as assessed by RT-PCR, whereas meningiomas express only the first two of these. Finally, elevated levels of [Ca2+]o and other polycationic CaR agonists dose dependently stimulate PTHrP secretion from HPA, astrocytomas, and meningiomas, although both basal and high [Ca2+]o-stimulated rates of PTHrP secretion are ~2.5-fold higher in HPA than in the glial tumors studied here. Therefore, our results show that HPA, astrocytomas, and meningiomas express both the CaR and PTHrP and that CaR agonists stimulate PTHrP secretion.
brain tumor; glioma; proliferation; humoral hypercalcemia of malignancy
This article has been cited by other articles:
|
|
 |
|
  M. Jenab, J. McKay, H. B. Bueno-de-Mesquita, F. J.B. van Duijnhoven, P. Ferrari, N. Slimani, E. H.J.M. Jansen, T. Pischon, S. Rinaldi, A. Tjonneland, et al. Vitamin D Receptor and Calcium Sensing Receptor Polymorphisms and the Risk of Colorectal Cancer in European Populations Cancer Epidemiol. Biomarkers Prev., September 1, 2009; 18(9): 2485 - 2491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Guerreiro, J. L. Renfro, D. M. Power, and A. V. M. Canario The parathyroid hormone family of peptides: structure, tissue distribution, regulation, and potential functional roles in calcium and phosphate balance in fish Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R679 - R696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chattopadhyay Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E761 - E770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. MacLeod, N. Chattopadhyay, and E. M. Brown PTHrP stimulated by the calcium-sensing receptor requires MAP kinase activation Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E435 - E442. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
