Xrcc2 Modulates Spontaneous and Radiation-Induced Tumorigenesis in Apc>min/+ Mice
Xrcc2 Modulates Spontaneous and Radiation-Induced Tumorigenesis in Apc>min/+ Mice
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DOI：
10.1158/1541-7786.mcr-10-0089
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发表时间：
2010-09-01
影响因子：
5.2
通讯作者：
Bouffler, Simon D.
中科院分区：
文献类型：
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作者：
Haines, Jackie W.;Coster, Margaret R.;Bouffler, Simon D.
XRCC 2在通过同源重组修复DNA损伤中具有重要作用。成年Apc（min/+）（min，多发性肠肿瘤）小鼠，野生型或Xrcc 2缺陷杂合子，假照射或2-戈伊X-照射。Apc（min/+）Xrcc 2（+/-）小鼠中自发性乳腺和肠道肿瘤的发生率低于Apc（min/+）Xrcc 2（+/+）小鼠（乳腺肿瘤：分别为14%和38%，chi（2）P = 0.03;达到完整寿命的小鼠中的肠道腺瘤：分别为108.6和130.1，t检验P = 0.005）。照射后，Xrcc 2杂合子雌性小鼠乳腺肿瘤的增加最大（Apc（min/+）Xrcc 2（+/-）小鼠为7.25 +/- 0.50倍，Apc（min/+）Xrcc 2（+/+）小鼠为2.57 +/- 0.35倍; t检验P < 0.001）。在Apc（min/+）Xrcc 2（+/-）小鼠中，照射后肠肿瘤多样性的增加显著更大（Apc（min/+）Xrcc 2（+/-），4.14 +/- 0.05倍，相对于Apc（min/+）Xrcc 2（+/+），3.30 +/- 0.05倍; t检验P < 0.001）。Apc（min/+）Xrcc 2（+/-）小鼠的肠肿瘤中所有18号染色体标记物的杂合性丢失均大于Apc（min/+）Xrcc 2（+/+）小鼠的肿瘤。这些发现表明，Xrcc 2单倍不足降低了Apc（min/+）背景下的自发肿瘤发生率，但增加了对辐射的致瘤反应。Mol Cancer Res; 8（9）; 1227-33.（C）2010年AACR。
XRCC2 has an important role in repair of DNA damage by homologous recombination. Adult Apc(min/+) (min, multiple intestinal neoplasia) mice, wild-type or heterozygous for Xrcc2 deficiency, were sham-irradiated or 2-Gy X-irradiated. Spontaneous mammary and intestinal tumor incidences are lower in Apc(min/+) Xrcc2(+/-) mice than in Apc(min/+) Xrcc2(+/+) mice (mammary tumors: 14% and 38%, respectively, chi(2) P = 0.03; intestinal adenomas in mice reaching full life span: 108.6 and 130.1, respectively, t-test P = 0.005). Following irradiation, the increase in mammary tumors was greatest in female mice heterozygous for Xrcc2 (7.25 +/- 0.50-fold in Apc(min/+) Xrcc2(+/-) mice compared with 2.57 +/- 0.35-fold in Apc(min/+) Xrcc2(+/+) mice; t-test P < 0.001). The increase in intestinal tumor multiplicity following irradiation was significantly greater in Apc(min/+) Xrcc2(+/-) mice (Apc(min/+) Xrcc2(+/-), 4.14 +/- 0.05-fold, versus Apc(min/+) Xrcc2(+/+), 3.30 +/- 0.05-fold; t-test P < 0.001). Loss of heterozygosity of all chromosome 18 markers was greater in intestinal tumors from Apc(min/+) Xrcc2(+/-) mice than in tumors from Apc(min/+) Xrcc2(+/+) mice. These findings indicate that Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apc(min/+) background but increases the tumorigenic response to radiation. Mol Cancer Res; 8(9); 1227-33. (C)2010 AACR.