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Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration

Abstract

The mouse parathyroid hormone-like hormone PthlhPro and PthlhThr variants are linked with susceptibility and resistance to skin carcinogenesis of Car-S and Car-R mice, respectively, and with in vitro effects (Oncogene, 19: 5324–5328, 2000). We have identified an additional Pthlh variant, consisting of Thr and three amino-acid changes in the C-terminus (PthlhSerAspTyr), carried by an evolutionarily distant Mus spretus (SPRET/Ei) inbred strain. When transfected into NCI-H520 tumor cells, this PthlhSerAspTyr variant did not stimulate tumor growth in nude mice. Analysis of cell adhesion, migration, and invasion patterns of PthlhPro-, PthlhThr-, and PthlhSerAspTyr-transfected NCI-H520 cells revealed a 1.5-fold decrease in adhesion efficiency on both collagen type I and Matrigel, and a 5–6-fold increase in migration capability in PthlhPro transfectants as compared to nontransfected, vector-transfected, PthlhThr-, or PthlhSerAspTyr-transfected cells. These findings suggest that the cancer modifier effects of the mouse Pthlh gene are mediated by differential cell adhesion and migration effects of PTHrP variants.

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Abbreviations

MMP:

matrix metals protease

Pthlh:

parathyroid hormone-like hormone gene

PTHrP:

parathyroid hormone-related protein

SNP:

single-nucleotide polymorphism

SQCC:

squamous cell carcinoma

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Acknowledgements

The support of the European Commission (Association Contracts FIGH-CT-1999-00006) and Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC, Italy) is gratefully acknowledged.

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Correspondence to Tommaso A Dragani.

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Benelli, R., Peissel, B., Manenti, G. et al. Allele-specific patterns of the mouse parathyroid hormone-related protein: influences on cell adhesion and migration. Oncogene 22, 7711–7715 (2003). https://doi.org/10.1038/sj.onc.1207088

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