Increased upstream methylation has no influence on the overexpression of the parathyroid hormone-related protein gene in squamous cell carcinoma of the lung
Increased upstream methylation has no influence on the overexpression of the parathyroid hormone-related protein gene in squamous cell carcinoma of the lung
Humoral hypercalcaemia of malignancy (HHM) commonly results from the excessive production of a parathyroid hormone-related protein (PTHrP) by tumours. We have previously shown malignancy is associated with increased DNA methylation in the 5' region of the PTHrP gene. In a series of patients with lung carcinoma and relatively high serum calcium levels, 3 patients showed substantially increased PTHrP gene methylation while 5 patients showed no change in methylation status in this region. Patients showed marked tumour-specific expression of PTHrP through the P1 and P3 promoters with more general tumour and non-tumour expression through the P2 promoter. The lack of potential key regulatory CpG sites in the P1 promoter and the complete demethylation in the P2 and P3 promoters suggests methylation does not influence tumour-specific expression of PTHrP. Although demethylation may be a prerequisite for P2 and P3 expression, the overexpression of the PTHrP gene in cancer cells must be mediated through mechanisms other than DNA methylation. Copyright (C) 2000 Elsevier Science Ltd.
DNA methylation, Parathyroid hormone-related protein, Promoter regions, Regulation of gene expression, Squamous cell carcinoma
2128-2136
Ganderton, R. H.
0cbaa3a4-8413-4a63-b48f-e582e14a2e35
Briggs, R. S.J.
a6b65ef0-e90c-4c07-bf5b-b70130c128b3
2000
Ganderton, R. H.
0cbaa3a4-8413-4a63-b48f-e582e14a2e35
Briggs, R. S.J.
a6b65ef0-e90c-4c07-bf5b-b70130c128b3
Ganderton, R. H. and Briggs, R. S.J.
(2000)
Increased upstream methylation has no influence on the overexpression of the parathyroid hormone-related protein gene in squamous cell carcinoma of the lung.
European Journal of Cancer, 36 (16), .
(doi:10.1016/S0959-8049(00)00294-X).
Abstract
Humoral hypercalcaemia of malignancy (HHM) commonly results from the excessive production of a parathyroid hormone-related protein (PTHrP) by tumours. We have previously shown malignancy is associated with increased DNA methylation in the 5' region of the PTHrP gene. In a series of patients with lung carcinoma and relatively high serum calcium levels, 3 patients showed substantially increased PTHrP gene methylation while 5 patients showed no change in methylation status in this region. Patients showed marked tumour-specific expression of PTHrP through the P1 and P3 promoters with more general tumour and non-tumour expression through the P2 promoter. The lack of potential key regulatory CpG sites in the P1 promoter and the complete demethylation in the P2 and P3 promoters suggests methylation does not influence tumour-specific expression of PTHrP. Although demethylation may be a prerequisite for P2 and P3 expression, the overexpression of the PTHrP gene in cancer cells must be mediated through mechanisms other than DNA methylation. Copyright (C) 2000 Elsevier Science Ltd.
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Published date: 2000
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Funding Information:
This work was funded by the Cancer Research Campaign. We would like to thank the following people for help with these studies; the Surgical and Pathology Department staff at Southampton General Hospital for the provision of tumour samples, Dr S.J. Cooke and Dr S.L. Zhang for provision of cultured cells, Dr M. Spanakis for help with statistical analysis, Dr A. Armston for providing chemical pathology data and Professor I.N.M. Day for his helpful comments on the manuscript. The BEN cell line was a gift from Professor A. Munro-Neville from the Ludwig Institute for Cancer Research.
Keywords:
DNA methylation, Parathyroid hormone-related protein, Promoter regions, Regulation of gene expression, Squamous cell carcinoma
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Local EPrints ID: 479038
URI: http://eprints.soton.ac.uk/id/eprint/479038
ISSN: 0959-8049
PURE UUID: c037e7cc-00d9-407d-92f1-4d53002d4bd1
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Date deposited: 19 Jul 2023 16:35
Last modified: 17 Mar 2024 13:24
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Author:
R. H. Ganderton
Author:
R. S.J. Briggs
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