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Gene Review

Pas1  -  pulmonary adenoma susceptibility 1

Mus musculus

Synonyms: Pas-1
 
 
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Disease relevance of Pas1

  • Appropriate crosses that include susceptible mice (Pas1(s)) provide a model system for identifying loci that can modify the lung cancer predisposition phenotype caused by Pas1 [1].
  • The mapping of Pas1 in mice stimulated us to test the possible association of genetic markers located in the homologous human region (12p12) with risk and prognosis of lung adenocarcinomas in man [1].
 

High impact information on Pas1

  • A functional switch from lung cancer resistance to susceptibility at the Pas1 locus in Kras2LA2 mice [2].
  • M. spretus mice (SPRET/Ei) carry a Pas1 resistance haplotype for chemically induced lung tumors [2].
  • 3. In Pas1/+ mice Par1 accounts for 23% of the phenotypic variance and 10 fold reduction in total tumour volume [3].
  • Pulmonary adenoma susceptibility 1 (Pas1), located on chromosome 6, is the major locus affecting inherited predisposition to lung tumor development in mice [4].
  • The Lrmp gene bears amino acid polymorphisms among various mouse strains that are highly correlated with the Pas1 allele status [5].
 

Biological context of Pas1

 

Anatomical context of Pas1

 

Associations of Pas1 with chemical compounds

  • In the present study, using (C3H x BALB)F1 x C3H backcross mice treated with urethane, we demonstrated that BALB mice possess the disease allele of the Pas1 gene despite their 15-fold more resistance relative to A/J mice (LOD = 22.6) [9].
  • A set of genes other than the pas genes governs the response to tumor modulation by butylated hydroxytoluene (BHT) [11].
 

Other interactions of Pas1

  • In addition, an interaction between the Pas1 and Pas2 QTLs was revealed [5].
  • Using this approach we have mapped the Pulmonary adenoma resistance 1 (Par1) locus that behaves like a modifier locus of Pas1 [1].
  • While the BALB Pas1 allele increased both the mean multiplicity and size of lung tumors, the BALB Par2 allele affected only the mean tumor multiplicity, implying that they are involved in different stages of multi-step lung carcinogenesis [9].
  • Pas1 candidate 1 (Pas1c1) gene (also named Lmna-rs1) was found to encode two alternatively spliced mRNA transcripts (i.e. Pas1c1-Va and Pas1c1-Vb) [12].
  • Mice with activated Ha-ras transgenes override the resistant pas alleles and are born with lung cancer [11].
 

Analytical, diagnostic and therapeutic context of Pas1

References

  1. Predisposition to lung tumorigenesis. Manenti, G., Nomoto, T., De Gregorio, L., Gariboldi, M., Stefania Falvella, F., Nagao, M., Dragani, T.A. Toxicol. Lett. (2000) [Pubmed]
  2. A functional switch from lung cancer resistance to susceptibility at the Pas1 locus in Kras2LA2 mice. To, M.D., Perez-Losada, J., Mao, J.H., Hsu, J., Jacks, T., Balmain, A. Nat. Genet. (2006) [Pubmed]
  3. Genetic mapping of a pulmonary adenoma resistance (Par1) in mouse. Manenti, G., Gariboldi, M., Elango, R., Fiorino, A., De Gregorio, L., Falvella, F.S., Hunter, K., Housman, D., Pierotti, M.A., Dragani, T.A. Nat. Genet. (1996) [Pubmed]
  4. Positional cloning of the major quantitative trait locus underlying lung tumor susceptibility in mice. Zhang, Z., Futamura, M., Vikis, H.G., Wang, M., Li, J., Wang, Y., Guan, K.L., You, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  5. Fine mapping and identification of candidate pulmonary adenoma susceptibility 1 genes using advanced intercross lines. Wang, M., Lemon, W.J., Liu, G., Wang, Y., Iraqi, F.A., Malkinson, A.M., You, M. Cancer Res. (2003) [Pubmed]
  6. Haplotype sharing suggests that a genomic segment containing six genes accounts for the pulmonary adenoma susceptibility 1 (Pas1) locus activity in mice. Manenti, G., Galbiati, F., Giannì-Barrera, R., Pettinicchio, A., Acevedo, A., Dragani, T.A. Oncogene (2004) [Pubmed]
  7. Pulmonary adenoma susceptibility 1 (Pas1) locus affects inflammatory response. Maria, D.A., Manenti, G., Galbiati, F., Ribeiro, O.G., Cabrera, W.H., Barrera, R.G., Pettinicchio, A., De Franco, M., Starobinas, N., Siqueira, M., Dragani, T.A., Ibañez, O.M. Oncogene (2003) [Pubmed]
  8. Assignment of a locus for mouse lung tumor susceptibility to proximal chromosome 19. Devereux, T.R., Wiseman, R.W., Kaplan, N., Garren, S., Foley, J.F., White, C.M., Anna, C., Watson, M.A., Patel, A., Jarchow, S. Mamm. Genome (1994) [Pubmed]
  9. Roles of the Pas1 and Par2 genes in determination of the unique, intermediate susceptibility of BALB/cByJ mice to urethane-induction of lung carcinogenesis: differential effects on tumor multiplicity, size and Kras2 mutations. Karasaki, H., Obata, M., Ogawa, K., Lee, G.H. Oncogene (1997) [Pubmed]
  10. Allelic effects of mouse Pas1 candidate genes in human lung cancer cell lines. Galbiati, F., Pettinicchio, A., Dragani, T.A., Manenti, G. Cancer Lett. (2006) [Pubmed]
  11. Genetic studies on lung tumor susceptibility and histogenesis in mice. Malkinson, A.M. Environ. Health Perspect. (1991) [Pubmed]
  12. Pas1c1 is a candidate for the mouse pulmonary adenoma susceptibility 1 locus. Wang, M., Futamura, M., Wang, Y., You, M. Oncogene (2005) [Pubmed]
  13. Pas1 haplotype-dependent genetic predisposition to lung tumorigenesis in rodents: a meta-analysis. Manenti, G., Dragani, T.A. Carcinogenesis (2005) [Pubmed]
 
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