Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems
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DOI：
10.1073/pnas.96.4.1563
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发表时间：
1999-02-16
影响因子：
11.1
通讯作者：
Parsons, R
中科院分区：
文献类型：
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作者：
Podsypanina, K;Ellenson, LH;Parsons, R
PTEN/Mmac1+/-杂合子小鼠表现出多个器官的肿瘤，包括子宫内膜、肝脏、前列腺、胃肠道、甲状腺和胸腺。在胸腺和肝脏肿瘤中发现野生型等位基因丢失。令人惊讶的是，胃肠道上皮肿瘤的发展与肠道淋巴组织有关。子宫内膜、甲状腺、前列腺和肝脏的肿瘤与淋巴组织无关，表现为高度有丝分裂。此外，这些小鼠有非肿瘤性淋巴结增生，这是由B细胞和巨噬细胞中检测到的凋亡遗传缺陷引起的。对与息肉相关的外周淋巴组织包括淋巴集合体的检查显示，杂合子动物的B细胞和T细胞的正常组织被破坏。综上所述，这些数据表明，PTEN是一种细胞凋亡和增殖的调节因子，在肠道中起到“景观”肿瘤抑制因子的作用，在其他器官中起到“把关人”肿瘤抑制因子的作用。
Pten/Mmac1 +/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs.