The Journal of clinical endocrinology and metabolism · 2005
Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene.
Клинический случайСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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VanHouten Joshua N, Yu Namyi, Rimm David, Dotto Jorge, Arnold Andrew, Wysolmerski John J, Udelsman Robert
Аннотация
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.
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.