Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene

J Clin Endocrinol Metab. 2006 Feb;91(2):580-3. doi: 10.1210/jc.2005-2095. Epub 2005 Nov 1.

Abstract

Context: The physiology of PTH is well described, but regulation of PTH gene expression remains enigmatic. This is, at least in part, because of a lack of suitable cell culture systems.

Objective, design, setting, patients, interventions, and main outcome measures: We report a case of severe hyperparathyroidism resulting from the ectopic production of PTH by a pancreatic malignancy. Cells from the primary tumor (PEPP1 cells) were established in culture to examine the etiology of ectopic PTH gene expression in this patient.

Results and conclusions: We failed to find amplification or rearrangement of the PTH gene but documented hypomethylation of the PTH promoter in tumor tissue. We found that PEPP1 cells support expression of a reporter gene containing regulatory sequences from the human PTH gene promoter. Therefore, this is the first report documenting ectopic PTH production by a tumor as the result of transactivation of the PTH gene. PEPP1 cells may be useful for future studies aimed at elucidating the details of PTH gene regulation.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • DNA Methylation
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • Fatal Outcome
  • Female
  • Gene Expression
  • Humans
  • Hypercalcemia / drug therapy
  • Hypercalcemia / genetics
  • Hypercalcemia / metabolism
  • Hyperparathyroidism / drug therapy
  • Hyperparathyroidism / genetics
  • Hyperparathyroidism / metabolism*
  • Neuroendocrine Tumors / genetics
  • Neuroendocrine Tumors / metabolism*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Parathyroid Glands / metabolism*
  • Parathyroid Glands / physiology
  • Parathyroid Hormone-Related Protein / biosynthesis*
  • Parathyroid Hormone-Related Protein / genetics*
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation

Substances

  • DNA, Neoplasm
  • Parathyroid Hormone-Related Protein