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Publication : The parathyroid hormone regulates skin tumour susceptibility in mice.

First Author  Okumura K Year  2017
Journal  Sci Rep Volume  7
Issue  1 Pages  11208
PubMed ID  28894263 Mgi Jnum  J:255758
Mgi Id  MGI:6109879 Doi  10.1038/s41598-017-11561-x
Citation  Okumura K, et al. (2017) The parathyroid hormone regulates skin tumour susceptibility in mice. Sci Rep 7(1):11208
abstractText  Using a forward genetics approach to map loci in a mouse skin cancer model, we previously identified a genetic locus, Skin tumour modifier of MSM 1 (Stmm1) on chromosome 7, conferring strong tumour resistance. Sub-congenic mapping localized Parathyroid hormone (Pth) in Stmm1b. Here, we report that serum intact-PTH (iPTH) and a genetic polymorphism in Pth are important for skin tumour resistance. We identified higher iPTH levels in sera from cancer-resistant MSM/Ms mice compared with susceptible FVB/NJ mice. Therefore, we performed skin carcinogenesis experiments with MSM-BAC transgenic mice (Pth (MSM)-Tg) and Pth knockout heterozygous mice (Pth (+/-)). As a result, the higher amounts of iPTH in sera conferred stronger resistance to skin tumours. Furthermore, we found that the coding SNP (rs51104087, Val28Met) localizes in the mouse Pro-PTH encoding region, which is linked to processing efficacy and increased PTH secretion. Finally, we report that PTH increases intracellular calcium in keratinocytes and promotes their terminal differentiation. Taken together, our data suggest that Pth is one of the genes responsible for Stmm1, and serum iPTH could serve as a prevention marker of skin cancer and a target for new therapies.
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