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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Abbreviations
- MMP:
-
matrix metals protease
- Pthlh:
-
parathyroid hormone-like hormone gene
- PTHrP:
-
parathyroid hormone-related protein
- SNP:
-
single-nucleotide polymorphism
- SQCC:
-
squamous cell carcinoma
References
Akino K, Ohtsuru A, Kanda K, Yasuda A, Yamamoto T, Akino Y, Naito S, Kurokawa M, Iwahori N and Yamashita S . (2000). Endocrinology, 141, 4313–4316.
Albini A . (1998). Pathol. Oncol. Res., 4, 230–241.
Albini A, Iwamoto Y, Kleinman HK, Martin GR, Aaronson SA, Kozlowski JM and McEwan RN . (1987). Cancer Res., 47, 3239–3245.
Bakre MM, Zhu Y, Yin H, Burton DW, Terkeltaub R, Deftos LJ and Varner JA . (2002). Nat. Med., 8, 995–1003.
Boccellino M, Biancone L, Cantaluppi V, Ye RD and Camussi G . (2000). J. Cell Physiol., 183, 254–264.
Cavallaro U and Christofori G . (2001). Biochim. Biophys. Acta, 1552, 39–45.
Conlan L, Martin T and Gillespie M . (2002). FEBS Lett., 527, 71–75.
de Miguel F, Fiaschi-Taesch N, Lopez-Talavera JC, Takane KK, Massfelder T, Helwig JJ and Stewart AF . (2001). Endocrinology, 142, 4096–4105.
Fassina G, Paglialunga G, Fontanini G, Cosimi A, Perrotta A, Aluigi M, Ardizzoni A and Albini A . (1996). Int. J. Oncol., 8, 253–261.
Goomer RS, Johnson KA, Burton DW, Amiel D, Maris TM, Gurjal A, Deftost LJ and Terkeltaub R . (2000). Endocrinology, 141, 4613–4622.
Kassis J, Lauffenburger DA, Turner T and Wells A . (2001). Semin. Cancer Biol., 11, 105–117.
Luparello C, Schilling T, Cirincione R and Pucci-Minafra I . (1999). FEBS Lett., 463, 265–269.
Manenti G, Peissel B, Gariboldi M, Falvella FS, Zaffaroni D, Allaria B, Pazzaglia S, Rebessi S, Covelli V, Saran A and Dragani TA . (2000). Oncogene, 19, 5324–5328.
Mercurio AM, Rabinovitz I and Shaw LM . (2001). Curr. Opin. Cell Biol., 13, 541–545.
Muller T, Bain G, Wang X and Papkoff J . (2002). Exp. Cell Res., 280, 119.
Nagase H, Mao JH and Balmain A . (1999). Proc. Natl. Acad. Sci. USA, 96, 15032–15037.
Postlethwaite AE, Snyderman R and Kang AH . (1976). J. Exp. Med., 144, 1188–1203.
Pupa SM, Menard S, Forti S and Tagliabue E . (2002). J. Cell. Physiol., 192, 259–267.
Rabbani SA . (2000). Int. J. Oncol., 16, 197–206.
Strewler GJ . (2000). N. Engl. J. Med., 342, 177–185.
Tovar Sepulveda VA, Shen X and Falzon M . (2002). Endocrinology, 143, 596–606.
Ye Y, Seitz PK and Cooper CW . (2001). Regul. Pept., 101, 19–23.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1207088
Keywords
This article is cited by
-
Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross
Mammalian Genome (2011)
-
Sequence divergence of Mus spretus and Mus musculus across a skin cancer susceptibility locus
BMC Genomics (2008)
-
Specific gene expression profiles distinguish among functional allelic variants of the mouse Pthlh gene in transfected human cancer cells
Oncogene (2006)