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A cancer modifier role for parathyroid hormone-related protein

Oncogene volume 19, pages 5324–5328 (2000)Cite this article

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.

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Acknowledgements

This work was funded in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) of Italy, and by grants from the European Commission (Association Contract No. F14PCT950008a).

GenBank: AJ278119.

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Authors and Affiliations

  1. Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy

    Giacomo Manenti, Bernard Peissel, Manuela Gariboldi, F Stefania Falvella, Daniela Zaffaroni & Tommaso A Dragani

  2. I.C.U., Istituto Nazionale Tumori, Milan, Italy

    Biagino Allaria

  3. ENEA CR Casaccia, Rome, Italy

    Simonetta Pazzaglia, Simonetta Rebessi, Vincenzo Covelli & Anna Saran

Authors
  1. Giacomo Manenti
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  2. Bernard Peissel
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  4. F Stefania Falvella
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  9. Vincenzo Covelli
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  10. Anna Saran
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  11. Tommaso A Dragani
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Manenti, G., Peissel, B., Gariboldi, M. et al. A cancer modifier role for parathyroid hormone-related protein. Oncogene 19, 5324–5328 (2000). https://doi.org/10.1038/sj.onc.1203916

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