A cancer modifier role for parathyroid hormone-related protein.
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.
Manenti
G
G
Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
Peissel
B
B
Gariboldi
M
M
Falvella
F S
FS
Zaffaroni
D
D
Allaria
B
B
Pazzaglia
S
S
Rebessi
S
S
Covelli
V
V
Saran
A
A
Dragani
T A
TA
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
C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins