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Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis

Abstract

Analysis of seven candidate genes mapping in the 1-Mb region of the mouse pulmonary adenoma resistance 4 (Par4) locus revealed a single amino-acid change, consisting in a nonconservative Arg968Cys variation in the juxtamembrane domain of the Met proto-oncogene-encoded protein. The BALB/c strain (resistant allele) carried the Arg allele, whereas the SWR/J mouse strain (Par4-susceptible allele) carried the Cys variation, recently proven to functionally modulate tumorigenesis. Seven genetic linkage crosses herein analysed and six crosses reported in the literature pointed to the candidacy of the Met gene for Par4. Analysis of genomic DNA of 126 lung adenocarcinoma patients for the Met juxtamembrane domain revealed the same Arg/Cys variation at the mouse homologous position in one patient; two other patients carried additional variants in the same domain, suggesting a potential role for rare MET juxtamembrane variants in human lung cancer.

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References

  • Biozzi G, Ribeiro OG, Saran A, Araujo ML, Maria DA, De Franco M, Cabrera WK, Sant'anna OA, Massa S, Covelli V, Mouton D, Neveu T, Siqueira M and Ibanez OM . (1998). Carcinogenesis, 19, 337–346.

  • De Gregorio L, Manenti G, Incarbone M, Pilotti S, Pastorino U, Pierotti MA and Dragani TA . (1998). Int. J. Cancer, 79, 269–272.

  • Devereux TR, Wiseman RW, Kaplan N, Garren S, Foley JF, White CM, Anna C, Watson MA, Patel A, Jarchow S, Maronpot RR and Anderson MW . (1994). Mamm. Genome, 5, 749–755.

  • Dragani TA . (2003). Cancer Res., 63, 3011–3018.

  • Festing MFW, Lin L, Devereux TR, Gao F, Yang A, Anna CH, White CM, Malkinson AM and You M . (1998). Genomics, 53, 129–136.

  • Gandino L, Longati P, Medico E, Prat M and Comoglio PM . (1994). J. Biol. Chem., 269, 1815–1820.

  • Gariboldi M, Manenti G, Canzian F, Falvella FS, Radice MT, Pierotti MA, Della Porta G, Binelli G and Dragani TA . (1993). Nat. Genet., 3, 132–136.

  • Gariboldi M, Spinola M, Milani S, Pignatiello C, Kadota K, Bono H, Hayashizaki Y, Dragani TA and Okazaki Y . (2003). Carcinogenesis, 24, 1819–1826.

  • Lee JH, Han SU, Cho H, Jennings B, Gerrard B, Dean M, Schmidt L, Zbar B and Vande Woude GF . (2000). Oncogene, 19, 4947–4953.

  • Lincoln SE, Daly M, Lander ES and Anonymous. (1992). Mapping genes controlling quantitative traits with MAPMAKER/QTL 1.1. Whitehead Institute Technical Report.

  • Longati P, Comoglio PM and Bardelli A . (2001). Curr. Drug Targets, 2, 41–55.

  • Ma PC, Kijima T, Maulik G, Fox EA, Sattler M, Griffin JD, Johnson BE and Salgia R . (2003). Cancer Res., 63, 6272–6281.

  • Manenti G, Acevedo A, Galbiati F, Giannì Barrera R, Noci S and Dragani TA . (2002). Int. J. Cancer, 99, 555–559.

  • Manenti G and Dragani TA . (2004). Carcinogenesis (in press).

  • Manenti G, Falvella FS, Gariboldi M, Dragani TA and Pierotti MA . (1995). Genomics, 29, 438–444.

  • Manenti G, Gariboldi M, Fiorino A, Zanesi N, Pierotti MA and Dragani TA . (1997a). Cancer Res., 57, 4164–4166.

  • Manenti G, Gariboldi M, Fiorino A, Zedda AI, Pierotti MA and Dragani TA . (1997b). Mamm. Genome, 8, 801–809.

  • Manenti G, Nomoto T, De Gregorio L, Gariboldi M, Stefania FF, Nagao M and Dragani TA . (2000). Toxicol. Lett., 112–113, 257–263.

  • Maria DA, Manenti G, Galbiati F, Ribeiro OG, Cabrera WK, Giannì Barrera R, Pettinicchio A, De Franco M, Starobinas N, Siqueira M, Dragani TA and Ibanez OM . (2003). Oncogene, 22, 426–432.

  • Obata M, Nishimori H, Ogawa K and Lee GH . (1996). Oncogene, 13, 1599–1604.

  • Peschard P, Fournier TM, Lamorte L, Naujokas MA, Band H, Langdon WY and Park M . (2001). Mol. Cell, 8, 995–1004.

  • Saran A, Neveu T, Covelli V, Mouton D, Pazzaglia S, Rebessi S, Doria G and Biozzi G . (2000). Int. J. Cancer, 88, 424–431.

  • Saran A, Zaffaroni D, Pazzaglia S, Peissel B, Galbiati F, Spinola M, Manenti G, Zanesi N, Rebessi S, Mancuso MT, Covelli V and Dragani TA . (2002). Int. J. Cancer, 97, 580–583.

  • Shultz KL, Donahue LR, Bouxsein ML, Baylink DJ, Rosen CJ and Beamer WG . (2003). J. Bone Mineral Res., 18, 175–185.

  • Weidner KM, Sachs M, Riethmacher D and Birchmeier W . (1995). Proc. Natl. Acad. Sci. USA, 92, 2597–2601.

  • Zhang Z, Lin L, Liu G, Wang M, Hill J, Wang Y, You M and Devereux TR . (2000). Exp. Lung Res., 26, 627–639.

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Acknowledgements

We thank Silvia Giordano for the gift of Met (B-2) antibody and GTL16 cells. This work was funded in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) and Compagnia di San Paolo, Torino, Italy, and from the European Commission (Association Contract No. F14PCT950008a).

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Correspondence to Tommaso A Dragani.

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Sequence data are available from GenBank under accession numbers AY439333, AY544984, AY551821, AY551822, AY558815, AY558816, AY558817, AY558818, AY558819, AY558820

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Zaffaroni, D., Spinola, M., Galvan, A. et al. Met proto-oncogene juxtamembrane rare variations in mouse and humans: differential effects of Arg and Cys alleles on mouse lung tumorigenesis. Oncogene 24, 1084–1090 (2005). https://doi.org/10.1038/sj.onc.1208324

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