A cancer modifier role for parathyroid hormone-related protein

• Published in: Oncogene Vol. 19; no. 47; pp. 5324 - 5328
• Main Authors: MANENTI, Giacomo, PEISSEL, Bernard, DRAGANI, Tommaso A, GARIBOLDI, Manuela, FALVELLA, F. Stefania, ZAFFARONI, Daniela, ALLARIA, Biagino, PAZZAGLIA, Simonetta, REBESSI, Simonetta, COVELLI, Vincenzo, SARAN, Anna
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 09-11-2000; Nature Publishing Group
• Subjects: Alleles; Amino acids; Animals; Base Sequence; Biological and medical sciences; Cancer; Carcinogenesis; Cell Division; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromosome 6; Chromosomes; Disease Susceptibility; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene mapping; Gene polymorphism; Genetic aspects; Genetic Predisposition to Disease - genetics; Haplotypes; Humans; Immunity, Innate - genetics; Mice; Mice, Nude; Molecular and cellular biology; Molecular Sequence Data; Morphology; Neoplasms, Squamous Cell - genetics; Oncogenes; osteostatin; Parathyroid; Parathyroid hormone; Parathyroid Hormone-Related Protein; Phenotype; Physiological aspects; Polymorphism; Polymorphism, Genetic; Proteins; Proteins - genetics; Proteins - physiology; Quantitative trait loci; Risk factors; Skin; Skin cancer; Skin Neoplasms - genetics; Squamous cell carcinoma; Transfection; Tumor Cells, Cultured; Tumorigenesis; Tumors; Italy; Skin disease; Vertebrata; Mammalia; Mouse; Rodentia; Parathyroid hormone related peptide; Tumor; Skin; Modifier gene; Carcinogenesis; Polymorphism
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203916

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.