Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen.

Parafibromin (PF) is a 531-amino acid protein encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal-dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of PF's overexpression on cell proliferation, we performed assays in four different cell lines. The transient overexpression of PF inhibited cell growth in HEK293 and NIH3T3 cells, but enhanced cell growth in the SV40 large T antigen-expressing cell lines such as 293FT and COS7 cells. In 293FT cells, PF was found to interact with SV40 large T antigen and its overexpression promoted entry into the S phase, implying that the interaction enhanced progression through the cell cycle. The tumor suppressor protein PF acts as a positive regulator of cell growth similar to an oncoprotein in the presence of SV40 large T antigen.

A case of hyperparathyroidism-jaw tumour syndrome found in the treatment of an ossifying fibroma in the maxillary bone.

Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is characterized by parathyroid tumours as well as by ossifying fibromas of the mandible and maxilla, renal cysts, or Wilms' tumours. Recently, the gene responsible for HPT-JT syndrome has been identified as the HRPT2 tumour suppressor gene. In an 18-year-old male, a tumour in the maxilla was first diagnosed as an ossifying fibroma. During biochemical screening before surgery, the patient received a diagnosis of primary hyperparathyroidism. Neck computed tomography scanning showed a parathyroid tumour. Surgical excisions to remove the jaw tumour and parathyroid adenoma were performed. The postoperative course has been uneventful and a follow up at 2 years revealed no evidence of recurrence. The HRPT2 germline mutation of 39delC was detected in the proband, but not in his unaffected parents. These results suggested that the germline mutation occurred de novo.