Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Oncogenomics
  • Published:

Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice

Oncogene volume 23, pages 4495–4504 (2004)Cite this article

Abstract

The pulmonary adenoma susceptibility 1 (Pas1) locus affects inherited predisposition and resistance to chemically induced lung tumorigenesis in mice. The A/J and C57BL/6J mouse strains carry the susceptibility and resistance allele, respectively. We identified and genotyped 65 polymorphisms in the Pas1 locus region in 29 mouse inbred strains, and delimited the Pas1 locus to a minimal region of 468 kb containing six genes. That region defined a core Pas1 haplotype with 42 tightly linked markers, including intragenic polymorphisms in five genes (Bcat1, Lrmp, Las1, Ghiso, and Kras2) and amino-acid changes in three genes (Lrmp, Las1, Lmna-rs1). In (A/J × C57BL/6J)F1 mouse lung tumors, the Lmna-rs1 gene was completely downregulated, whereas allele-specific downregulation of the C57BL/6J-derived allele was observed at the Las1 gene, suggesting the potential role of these genes in tumor suppression. These results indicate a complex multigenic nature of the Pas1 locus, and point to a functional role for both intronic and exonic polymorphisms of the six genes of the Pas1 haplotype in lung tumor susceptibility.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Akamatsu Y . (1975). J. Natl. Cancer Inst., 55, 893–897.

  • Askling J, Grunewald J, Eklund A, Hillerdal G and Ekbom A . (1999). Am. J. Respir. Crit. Care Med., 160, 1668–1672.

  • Bauer AK, Dwyer-Nield LD, Keil K, Koski K and Malkinson AM . (2001). Exp. Lung Res., 27, 197–216.

  • Behrens TW, Jagadeesh J, Scherle P, Kearns G, Yewdell J and Staudt LM . (1994). J. Immunol., 153, 682–690.

  • Brownson RC and Alavanja MC . (2000). Cancer Causes Control, 11, 853–858.

  • Burkhard P, Stetefeld J and Strelkov SV . (2001). Trends Cell Biol., 11, 82–88.

  • Cormier R, Hong K, Halberg R, Hawkins T, Richardson P, Mulherkar R, Dove W and Lander ES . (1997). Nat. Genet., 17, 88–91.

  • Cormier RT, Bilger A, Lillich AJ, Halberg RB, Hong KH, Gould KA, Borenstein N, Lander ES and Dove WF . (2000). Oncogene, 19, 3182–3192.

  • Darvasi A and Pisante-Shalom A . (2002). Trends Genet., 18, 489–491.

  • De Luca M, Roshina NV, Geiger-Thornsberry GL, Lyman RF, Pasyukova EG and Mackay TF . (2003). Nat. Genet., 34, 429–433.

  • 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.

  • Eden A and Benvenisty N . (1999). FEBS Lett., 457, 255–261.

  • Festing MFW, Yang A and Malkinson AM . (1994). Genet. Res., 64, 99–106.

  • 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.

  • Hanahan D and Weinberg RA . (2000). Cell, 100, 57–70.

  • Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA and Jacks T . (2001). Nature, 410, 1111–1116.

  • Kawakami K, Salonga D, Park JM, Danenberg KD, Uetake H, Brabender J, Omura K, Watanabe G and Danenberg PV . (2001). Clin. Cancer Res., 7, 4096–4101.

  • Liang T, Spence J, Liu L, Strother WN, Chang HW, Ellison JA, Lumeng L, Li TK, Foroud T and Carr LG . (2003). Proc. Natl. Acad. Sci. USA, 100, 4690–4695.

  • Malkinson AM . (1989). Toxicology, 54, 241–271.

  • Malkinson AM and Beer DS . (1984). J. Natl. Cancer Inst., 73, 925–933.

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

  • Manenti G, Stafford A, De Gregorio L, Gariboldi M, Falvella FS, Avner P and Dragani TA . (1999). Genome Res., 9, 639–646.

  • 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.

  • Mayne ST, Buenconsejo J and Janerich DT . (1999). Am. J. Epidemiol., 149, 13–20.

  • Re FC, Manenti G, Borrello MG, Colombo MP, Fisher JH, Pierotti MA, Della Porta G and Dragani TA . (1992). Mol. Carcinogen., 5, 155–160.

  • Shaughnessy Jr JD, Largaespada DA, Tian E, Fletcher CF, Cho BC, Vyas P, Jenkins NA and Copeland NG . (1999). Oncogene, 18, 2069–2084.

  • Steinmetz LM, Sinha H, Richards DR, Spiegelman JI, Oefner PJ, McCusker JH and Davis RW . (2002). Nature, 416, 326–330.

  • Trainin N, Linker-Israeli M, Small M and Boiato-Chen L . (1967). Int. J. Cancer, 2, 326–336.

  • Wade CM, Kulbokas III EJ, Kirby AW, Zody MC, Mullikin JC, Lander ES, Lindblad-Toh K and Daly MJ . (2002). Nature, 420, 574–578.

  • Wang M, Lemon WJ, Liu G, Wang Y, Iraqi FA, Malkinson AM and You M . (2003). Cancer Res., 63, 3317–3324.

  • Webb KE, Martin JF, Cotton J, Erusalimsky JD and Humphries SE . (2003). Exp. Hematol., 31, 488–494.

  • Wiltshire T, Pletcher MT, Batalov S, Barnes SW, Tarantino LM, Cooke MP, Wu H, Smylie K, Santrosyan A, Copeland NG, Jenkins NA, Kalush F, Mural RJ, Glynne RJ, Kay SA, Adams MD and Fletcher CF . (2003). Proc. Natl. Acad. Sci. USA, 100, 3380–3385.

  • Zhang Z, Futamura M, Vikis HG, Wang M, Li J, Wang Y, Guan KL and You M . (2003). Proc. Natl. Acad. Sci. USA, 100, 12642–12647.

  • Zhang Z, Wang Y, Vikis HG, Johnson L, Liu G, Li J, Anderson MW, Sills RC, Hong HL, Devereux TR, Jacks T, Guan KL and You M . (2001). Nat. Genet., 29, 25–33.

Download references

Acknowledgements

This work was funded in part by grants from Associazione and Fondazione Italiana Ricerca Cancro (AIRC and FIRC).

Author information

Authors and Affiliations

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

    Giacomo Manenti, Federica Galbiati, Roberto Giannì-Barrera, Angela Pettinicchio & Tommaso A Dragani

  2. Facultad de Medicina, Universidad de La Laguna, Tenerife, Spain

    Abraham Acevedo

Authors
  1. Giacomo Manenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Federica Galbiati
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roberto Giannì-Barrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angela Pettinicchio
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abraham Acevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tommaso A Dragani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tommaso A Dragani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Manenti, G., Galbiati, F., Giannì-Barrera, R. et al. Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice. Oncogene 23, 4495–4504 (2004). https://doi.org/10.1038/sj.onc.1207584

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207584

Keywords

This article is cited by

Search

Advanced search

Quick links