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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb~+/- mice
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RB-mediated suppression of spontaneous multiple neuroendocrine neoplasia and lung metastases in Rb~+/- mice

机译：RB介导的Rb〜+/-小鼠自发性多发性神经内分泌肿瘤和肺转移的抑制

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摘要

Alterations in pathways mediated by retino- blastoma susceptibility gene (RB) product are among the most common in human cancer. Mice with a single copy of the Rb gene are shown to develop a syndrome of multiple neuroen- docrine neoplasia. The earliest Rb-deficient atypical cells were identified in the intermediate and anterior lobes of the pituitary, the thyroid and parathyroid glands, and the adrenal medulla within the first 3 months of postnatal development. These cells form gross tumors with various degrees of malig- nancy by postnatal day 350. By age of 380 days, 84 of Rb~+/- mice exhibited lung metastases from C-cell thyroid carcino- mas. Expression of a human RB transgene in the Rb~+/- mice suppressed carcinogenesis in all tissues studied. Of particular clinical relevance, the frequency of lung metastases also was reduced to 12 in Rb~+/- mice by repeated i.v. administration of lipid-entrapped, polycation-condensed RB complementary , DNA. Thus, in spite of long latency periods during which secondary alterations can accumulate, the initial loss of Rb function remains essential for tumor progression in multiple types of neuroendocrine cells. Restoration of RB function in humans may prove an effective general approach to the treatment of RB-deficient disseminated tumors.
机译：视网膜母细胞瘤易感基因（RB）产物介导的途径改变在人类癌症中最为常见。显示具有Rb基因单拷贝的小鼠发展为多发神经内分泌肿瘤。在出生后前三个月内，在垂体的中叶和前叶，甲状腺和甲状旁腺以及肾上腺髓质中发现了最早的缺乏Rb的非典型细胞。到出生后第350天，这些细胞就形成了各种程度的恶性肿瘤。到380天时，已有84例Rb〜+/-小鼠表现出C细胞甲状腺癌的肺转移。 Rb〜+/-小鼠中人RB转基因的表达抑制了所有研究组织的致癌作用。具有特殊临床意义的是，通过反复静脉内注射，Rb〜+/-小鼠的肺转移频率也降低到了12。脂质包裹，聚阳离子缩合的RB互补DNA的给药。因此，尽管潜伏期长，继发性改变可以累积，但Rb功能的初始丧失对于多种类型的神经内分泌细胞的肿瘤进展仍然至关重要。恢复人的RB功能可能是治疗RB缺乏的弥散性肿瘤的有效通用方法。

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