title: A cancer modifier role for parathyroid hormone-related protein.
abstract: 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.
authors: Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
authors: G
authors: G
authors: Manenti
authors: B
authors: B
authors: Peissel
authors: M
authors: M
authors: Gariboldi
authors: F S
authors: FS
authors: Falvella
authors: D
authors: D
authors: Zaffaroni
authors: B
authors: B
authors: Allaria
authors: S
authors: S
authors: Pazzaglia
authors: S
authors: S
authors: Rebessi
authors: V
authors: V
authors: Covelli
authors: A
authors: A
authors: Saran
authors: T A
authors: TA
authors: Dragani
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D004198:Disease Susceptibility; D015870:Gene Expression; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D018307:Neoplasms, Squamous Cell / Q000235:genetics*; D044162:Parathyroid Hormone-Related Protein; D010641:Phenotype; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D012878:Skin Neoplasms / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins