Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains
Cancer modifier alleles inhibiting lung tumorigenesis are common in inbred mouse strains
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DOI：
10.1002/ijc.10386
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发表时间：
2002-06-01
影响因子：
6.4
通讯作者：
Dragani, TA
中科院分区：
文献类型：
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作者：
Manenti, G;Acevado, A;Dragani, TA
近交系小鼠肺肿瘤易感性是由肺腺瘤易感性I(PASI(S))基因座的易感等位基因引起的。然而，在乌拉坦治疗后，大多数携带PASI(S)等位基因的菌株显示出中等(1-4个肿瘤/小鼠)而不是高度敏感(15-30个肿瘤/小鼠)的肺癌表型。为了验证肺腺瘤耐药(PAR)基因座携带显性或共显性抗性等位基因的假设，我们将对肺部肿瘤发生具有中等易感性或抗药性的小鼠与高度敏感的A/J品系进行杂交。11个F-1杂交种用乌拉坦诱导肺肿瘤形成。由于PASI等位基因的剂量效应，A/J株每只小鼠产生了35.3个肿瘤，而它与C57BL/6J小鼠(PAR基因座的零等位基因)的F-1杂交产生了22.8个肿瘤/只。与A/J和(A/J×C57BL/6J)小鼠相比，品系129/SVJ、CBA/J、ST/J和LP/J(PASI(S))和SPW、DBA/2J和C57L/J(PASI(R))小鼠的F-1杂交种对肺肿瘤的多样性(即每只小鼠0.3-12.8个肿瘤)显著降低。这些结果表明，PAR基因座上的抗性等位基因在近交系小鼠中很常见，并解释了携带PASI(S)等位基因的品系的肺肿瘤发生中间表型。(C)2002年Wiley-Liss，Inc.
Lung tumor susceptibility in inbred mouse strains is caused by the susceptibility allele at the pulmonary adenoma susceptibility I (PasI(s)) locus. However, after urethane treatment, most strains carrying the PasI(s) allele show an intermediate (1-4 tumors/mouse) instead of a highly susceptible (15-30 tumors/mouse) lung tumor phenotype. To test the hypothesis that strains displaying the intermediate lung tumor phenotype carry dominant or codominant resistance alleles at pulmonary adenoma resistance (Par) loci, we crossed mice of intermediate susceptibility or resistance to lung tumorigenesis with the highly susceptible A/J strain. Eleven F-1 hybrids were treated with urethane to induce lung tumorigenesis. The A/J strain developed 35.3 tumors/mouse, while its F-1 hybrid with C57BL/6J mice (null allelle at Par loci) developed 22.8 tumors/mouse due to the PasI allele dosage effect. F-1 hybrids of strains 129/SvJ, CBA/J, ST/J and LP/J (PasI(s)) and of SPW, DBA/2J and C57L/J (PasI(r)) mice showed significant reduction in lung tumor multiplicity (i.e., 0.3-12.8 tumors/mouse) compared to A/J and (A/J X C57BL/6J), mice. These results indicate that resistance alleles at Par loci are common in inbred mouse strains and account for the lung tumorigenesis intermediate phenotype of strains carrying the PasI(s) allele. (C) 2002 Wiley-Liss, Inc.