フクコウジョウセン キノウ コウシンショウ : ガク シュヨウ ショウコウグン
Hyperparathyroidism : Jaw Tumor Syndrome
Yoshimoto, Katsuhiko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Mizusawa, Noriko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Iwata, Takeo Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School KAKEN Search Researchers
Ono, Shinji Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School
The hyperparathyroidism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder characterized by the occurrence of parathyroid tumors in association with ossifying fibromas of the maxilla and/or mandible. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. Ossifying fibroma occurs in about 30% of individuals with HPT-JT syndrome. Many patients with HPT-JT syndrome present with a single benign parathyroid tumor; however, the optimal surgical approach to primary hyperparathyroidism has not yet been established. The gene responsible for HPT-JT syndrome on 1q31.2, known as CDC73 (formerly known as HRPT2), was identified and encodes a 531-amino acid protein known as parafibromin. Germline CDC73 mutations are detected in patients with HPT-JT syndrome, and majority (>75%) of mutations predict premature truncation of the parafibromin, and the demonstration of loss of heterozygosity at the CDC73 locus in tumors is consistent with a tumor suppressor role. Approximately 20% of patients with apparently sporadic parathyroid cancer are found to have germline CDC73 mutations, suggesting that such cases may, in fact, represent undiagnosed HPT-JT syndrome. Parafibromin is known to act as a tumor suppressor that inhibits expression of cyclin D1 and c-myc by recruiting histone methyltransferase. On the other hand, parafibromin can act in the opposing direction by binding β-catenin, thereby activating oncogenic Wnt signaling. Furthermore, parafibromin acts as a positive regulator of cell growth similar to an oncoprotein in the presence of SV40 large T antigen. These results suggest the context-dependent oncogenic or tumor- suppressor functions of parafibromin.
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