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. Pthlh(THr) and Pthlh(Pro) 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 Pthlh(Pro) 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 Pthlh(Thr)-transfected cells. These results point to the role of the Pthlh gene as a cancer modifier gene in skin tumorigenesis.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cancer Research
Manenti, G., Peissel, B., Gariboldi, M., Falvella, F. S., Zaffaroni, D., Allaria, B., ... Dragani, T. A. (2000). A cancer modifier role for parathyroid hormone-related protein. Oncogene, 19(47), 5324 - 5328. https://doi.org/10.1038/sj.onc.1203916