ID 109648
Author
Imanishi, Yasuo University of Connecticut School of Medicine
Schipani, Ernestina Massachusetts General Hospital
Mallya, Sanjay University of Connecticut School of Medicine
Papanikolaou, Alexandros University of Connecticut School of Medicine
Kifor, Olga Brigham and Women’s Hospital
Tokura, Takehiko University of Connecticut School of Medicine
Sablosky, Marilyn University of Connecticut School of Medicine
Ledgard, Felicia University of Connecticut School of Medicine
Gronowicz, Gloria University of Connecticut School of Medicine
Wang, Timothy C. Massachusetts General Hospital
Schmidt, Emmett V. Massachusetts General Hospital
Hall, Charles University of Connecticut School of Medicine
Brown, Edward M. Brigham and Women’s Hospital
Bronson, Roderick US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University
Arnold, Andrew University of Connecticut School of Medicine
Content Type
Journal Article
Description
The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin D1’s role in parathyroid tumorigenesis. Parathyroid hormone gene regulatory region–cyclin D1 (PTH–cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH. Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways can cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder.
Journal Title
Journal of Clinical Investigation
ISSN
00219738
NCID
AA00695520
Volume
107
Issue
9
Start Page
1093
End Page
1102
Sort Key
1093
Published Date
2001-05
Remark
Copyright © 2001, American Society for Clinical Investigation
EDB ID
Published Source
Journal of Clinical Investigation (2001) Vol.107 No.9 p.1093–1102 (doi: 10.1172/JCI10523)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences