Genetic prevention of lymphoma in p53 knockout mice allows the early development of p53-related sarcomas.
Genetic prevention of lymphoma in p53 knockout mice allows the early development of p53-related sarcomas.
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DOI：
10.18632/oncotarget.2650
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发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Lollini PL
中科院分区：
文献类型：
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作者：
Landuzzi L;Ianzano ML;Nicoletti G;Palladini A;Grosso V;Ranieri D;Dall'Ora M;Raschi E;Laranga R;Gambarotti M;Picci P;De Giovanni C;Nanni P;Lollini PL
在小鼠中，P53基因的纯合敲除会导致淋巴瘤的早期死亡，几乎完全外显性，从而阻碍了与P53改变相关的其他肿瘤组织类型的研究。为了避免淋巴瘤的发生，我们将P53基因敲除小鼠(BALB-P53小鼠)与淋巴细胞BALB/c Rag2−/−；IL2RG−/−(RGKO)小鼠杂交。我们比较了纯合子(BALB-P53−/−)和杂合子(BALB-P53+/−)小鼠与淋巴细胞小鼠(RGKO-P53−/−和RGKO-P53+/−)的肿瘤光谱。淋巴瘤发生率在BALB-P53−/−小鼠中超过80%，而在RGKO-P53−/−小鼠中显著降低。RGKO-P53−/−小鼠的常见肿瘤是血管肉瘤(男女发病率均在65%以上，平均潜伏期为18周)，其他肿瘤包括软组织肉瘤(发病率~10%)、肺癌和乳腺癌。P53杂合子也有肿瘤谱改变，其中淋巴瘤相对罕见(~20%)。RGKO-P53+/−组血管肉瘤发生率增加，达30%，女性骨肉瘤发生率增加，达20%。骨肉瘤与相应的人类肿瘤一样，具有累及四肢的特点和较高的转移能力，主要转移到肺部。P53相关基因(p16INK4a、p19Arf、p15INK4b、p21Cip1)表达有特异性改变。在p53基因敲除小鼠中，淋巴瘤的基因预防导致了肉瘤发展的新模型，可用于血管肉瘤和骨肉瘤发病和转移的研究。
Homozygous knockout of p53 in mice leads to early mortality from lymphoma, with almost complete penetrance, thus hampering studies of other tumor histotypes related to p53 alterations. To avoid lymphoma development, we crossed p53 knockout mice (BALB-p53 mice) with alymphocytic BALB/c Rag2−/−;Il2rg−/− (RGKO) mice. We compared the tumor spectrum of homozygous (BALB-p53−/−) and heterozygous (BALB-p53+/−) mice with alymphocytic mice (RGKO-p53−/− and RGKO-p53+/−). Lymphoma incidence in BALB-p53−/− mice exceeded 80%, whereas in RGKO-p53−/− it was strongly reduced. The prevalent tumor of RGKO-p53−/− mice was hemangiosarcoma (incidence over 65% in both sexes, mean latency 18 weeks), other tumors included soft tissue sarcomas (incidence ~10%), lung and mammary carcinomas. Tumor spectrum changes occurred also in p53 heterozygotes, in which lymphomas are relatively rare (~20%). RGKO-p53+/− had an increased incidence of hemangiosarcomas, reaching ~30%, and females had an increased incidence of osteosarcomas, reaching ~20%. Osteosarcomas shared with the corresponding human tumors the involvement of limbs and a high metastatic ability, mainly to the lungs. Specific alterations in the expression of p53-related genes (p16Ink4a, p19Arf, p15Ink4b, p21Cip1) were observed. Genetic prevention of lymphoma in p53 knockout mice led to new models of sarcoma development, available for studies on hemangiosarcoma and osteosarcoma onset and metastatization.
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影响因子：
64.8
作者：
Martins, Vera C.;Busch, Katrin;Rodewald, Hans-Reimer
通讯作者：
Rodewald, Hans-Reimer
影响因子：
64.8
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
通讯作者：
BRADLEY, A
影响因子：
3.6
作者：
Leontieva, Olga V.;Novototskaya, Liliya R.;Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.
在没有T细胞受体重排的情况下，p53防止了胸腺细胞分化的CD4+ CD8+阶段的成熟。
影响因子：
15.3
作者：
Di, JA;Lenardo, MJ;ZunigaPflucker, JC
通讯作者：
ZunigaPflucker, JC
影响因子：
--
作者：
Jones KB
通讯作者：
Jones KB