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.

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