The role of DNA methylation in the expression of parathyroid hormone-related protein in humoral hypercalcemia of malignancy

Published on Feb 1, 1993in Biochemical Society Transactions5.407
· DOI :10.1042/BST021011S
Rosalind H. Ganderton5
Estimated H-index: 5
(Southampton General Hospital),
Roger Briggs17
Estimated H-index: 17
(Southampton General Hospital)
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Abstract
Hypercalcaemia is a complication in approximately 10% of malignant disorders and is particularly common in patients with tumours of epithelial origin [l]. In a ,high proportion of these patients the hypercalcaemia is due to the production of parathyroid hormone-related protein (PTHrP) [2]. This peptide has strong homology to PTH at the N-terminus [3] and closely mimics the action of PTH by binding to the same receptor [4]. Since the isolation of PTHrP from tumours associated with humoral hypercalcaemia of malignancy, PTHrP has been found to be expressed in a wide range of normal tissue. Suggested roles in nature vary from maintaining calcium homeostasis in the neonate [5] to a general modulating role in cell growth and differentiation
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#1Rosalind H. Ganderton (Southampton General Hospital)H-Index: 5
#2Roger Briggs (Southampton General Hospital)H-Index: 17
Abstract Excessive production of a parathyroid hormone-related protein (PTHrP) by tumours commonly results in the syndrome of humoral hypercalcaemia of malignancy. We have investigated whether epigenetic changes play a role in over-expression of the PTHrP gene, using cultures lung cells as a model system. Study of the methylation status of CpG dinucleotides in the 5′ region of the gene showed that in normal cells the CpG island was completely unmethylated. In the lung squamous cell carcinoma cel...
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