title: Hypercalcemia of malignancy due to ectopic transactivation of the parathyroid hormone gene.
abstract: BACKGROUND
  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.
  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.
  
  
  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.
authors.affiliation: Section of Endocrinology and Metabolism, Department of Medicine, Yale University School of Medicine, TAC S131, 333 Cedar Street, New Haven, CT 06520-8020, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: VanHouten
authors.forename: Namyi
authors.initials: N
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Rimm
authors.forename: Jorge
authors.initials: J
authors.lastname: Dotto
authors.forename: Andrew
authors.initials: A
authors.lastname: Arnold
authors.forename: John J
authors.initials: JJ
authors.lastname: Wysolmerski
authors.forename: Robert
authors.initials: R
authors.lastname: Udelsman
mesh_terms: D000368:Aged; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D015870:Gene Expression; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006961:Hyperparathyroidism / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D010280:Parathyroid Glands / Q000378:metabolism* / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation
chemical_list: D004273:DNA, Neoplasm; D044162:Parathyroid Hormone-Related Protein