Open AccessA cancer modifier role for parathyroid hormone-related protein
Author(s) -
Giacomo Manenti,
Bernard Peissel,
Manuela Gariboldi,
Felicia Stefania Falvella,
Daniela Zaffaroni,
Biagino Allaria,
Simonetta Pazzaglia,
Simonetta Rebessi,
Vincenzo Covelli,
Anna Saran,
Tommaso A. Dragani
Publication year - 2000
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/sj.onc.1203916
Subject(s) - biology , carcinogenesis , transfection , allele , locus (genetics) , gene , parathyroid hormone related protein , cancer research , microbiology and biotechnology , genetics , parathyroid hormone , medicine , calcium
The parathyroid hormone-related protein (PTHrP) gene (Pthlh) maps in the distal region of mouse chromosome 6 that contains a quantitative trait locus associated with genetic predisposition to skin tumorigenesis. Here, we report a genetic polymorphism located in the osteostatin encoding region of the Pthlh gene and that produces Thr/ Pro PTHrP variants. PthlhThr and PthlhPro alleles were significantly linked with resistance and susceptibility to skin carcinogenesis in phenotypically selected Car-R and Car-S outbred mice. Transfection of human NCI-H520 squamous cell carcinoma cells with the PthlhPro allele resulted in cells growing in clusters, tending to pile up, and growing at a significantly faster rate in nude mice than non-transfected and PthlhThr-transfected cells. These results point to the role of the Pthlh gene as a cancer modifier gene in skin tumorigenesis.