Please use this identifier to cite or link to this item: https://doi.org/10.1038/onc.2017.43
Title: Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: Model for the hyperparathyroidism-jaw tumour syndrome
Authors: Walls, G.V
Stevenson, M
Lines, K.E
Newey, P.J
Reed, A.A.C
Bowl, M.R
Jeyabalan, J
Harding, B
Bradley, K.J
Manek, S
Chen, J
Wang, P
Williams, B.O
Teh, B.T 
Thakker, R.V
Keywords: calcium
galectin 3
parathyroid hormone
progesterone receptor
HRPT2 protein, mouse
tumor suppressor protein
adenofibroma
adenomyoma
allele
animal cell
animal experiment
animal tissue
Article
binding site
calcium blood level
carcinogenesis
cell division
cell proliferation
cell survival
controlled study
crossing over
exon
female
hyperparathyroidism
in vitro study
in vivo study
jaw tumor
male
mammal cell
mouse
nonhuman
parathyroid adenoma
parathyroid gland
parathyroid hormone blood level
priority journal
protein expression
squamous cell metaplasia
stop codon
tumor syndrome
uterus cancer
uterus tissue
Western blotting
wild type
adenoma
animal
C57BL mouse
carcinoma
complication
fibroma
gene deletion
genetics
hyperparathyroidism
jaw tumor
knockout mouse
parathyroid tumor
uterus cancer
Adenoma
Animals
Carcinoma
Female
Fibroma
Gene Deletion
Hyperparathyroidism
Jaw Neoplasms
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Parathyroid Neoplasms
Tumor Suppressor Proteins
Uterine Neoplasms
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Walls, G.V, Stevenson, M, Lines, K.E, Newey, P.J, Reed, A.A.C, Bowl, M.R, Jeyabalan, J, Harding, B, Bradley, K.J, Manek, S, Chen, J, Wang, P, Williams, B.O, Teh, B.T, Thakker, R.V (2017). Mice deleted for cell division cycle 73 gene develop parathyroid and uterine tumours: Model for the hyperparathyroidism-jaw tumour syndrome. Oncogene 36 (28) : 4025-4036. ScholarBank@NUS Repository. https://doi.org/10.1038/onc.2017.43
Rights: Attribution 4.0 International
Abstract: The hyperparathyroidism-jaw tumour (HPT-JT) syndrome is an autosomal dominant disorder characterized by occurrence of parathyroid tumours, often atypical adenomas and carcinomas, ossifying jaw fibromas, renal tumours and uterine benign and malignant neoplasms. HPT-JT is caused by mutations of the cell division cycle 73 (CDC73) gene, located on chromosome 1q31.2 and encodes a 531 amino acid protein, parafibromin. To facilitate in vivo studies of Cdc73 in tumourigenesis we generated conventional (Cdc73+/-) and conditional parathyroid-specific (Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre) mouse models. Mice were aged to 18-21 months and studied for survival, tumour development and proliferation, and serum biochemistry, and compared to age-matched wild-type (Cdc73+/+ and Cdc73+/+/PTH-Cre) littermates. Survival of Cdc73+/- mice, when compared to Cdc73+/+ mice was reduced (Cdc73+/- =80%; Cdc73+/+ =90% at 18 months of age, P<0.05). Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice developed parathyroid tumours, which had nuclear pleomorphism, fibrous septation and increased galectin-3 expression, consistent with atypical parathyroid adenomas, from 9 months of age. Parathyroid tumours in Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice had significantly increased proliferation, with rates >fourfold higher than that in parathyroid glands of wild-type littermates (P<0.0001). Cdc73+/-, Cdc73+/L/PTH-Cre and Cdc73L/L/PTH-Cre mice had higher mean serum calcium concentrations than wild-type littermates, and Cdc73+/- mice also had increased mean serum parathyroid hormone (PTH) concentrations. Parathyroid tumour development, and elevations in serum calcium and PTH, were similar in males and females. Cdc73+/- mice did not develop bone or renal tumours but female Cdc73+/- mice, at 18 months of age, had uterine neoplasms comprising squamous metaplasia, adenofibroma and adenomyoma. Uterine neoplasms, myometria and jaw bones of Cdc73+/- mice had increased proliferation rates that were 2-fold higher than in Cdc73+/+ mice (P<0.05). Thus, our studies, which have established mouse models for parathyroid tumours and uterine neoplasms that develop in the HPT-JT syndrome, provide in vivo models for future studies of these tumours. © The Author(s) 2017.
Source Title: Oncogene
URI: https://scholarbank.nus.edu.sg/handle/10635/179192
ISSN: 09509232
DOI: 10.1038/onc.2017.43
Rights: Attribution 4.0 International
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