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首页> 外文期刊>Oncogene >Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2|[sol]|Neu-induced tumors
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Sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of ErbB2|[sol]|Neu-induced tumors

机译：持续的乳腺营养足以促进和同步ErbB2 | [sol] | Neu诱导的肿瘤的发展

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Epidemiological studies indicate that parity enhances HER2/ErbB2/Neu-induced breast tumorigenesis. Furthermore, recent studies using multiparous, ErbB2/Neu-overexpressing mouse mammary tumor virus (MMTV-Neu) mice have shown that parity induces a population of cells that are targeted for ErbB2/Neu-induced transformation. Although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous MMTV-Neu mice remains stochastic, suggesting that additional events are required for ErbB2/Neu to cause mammary tumors. Whether such events are genetic in nature or reflective of the dynamic hormonal control of the gland that occurs with pregnancy remains unclear. We postulated that young age at pregnancy initiation or chronic trophic maintenance of mammary epithelial cells might provide a cellular environment that significantly increases susceptibility to ErbB2/Neu-induced tumorigenesis. MMTV-Neu mice that were maintained pregnant or lactating beginning at 3 weeks of age demonstrated accelerated tumorigenesis, but this process was still stochastic, indicating that early pregnancy does not provide the requisite events of tumorigenesis. However, bitransgenic mice that were generated by breeding MMTV-Neu mice with a luteinizing hormone-overexpressing mouse model of ovarian hyperstimulation developed multifocal mammary tumors in an accelerated, synchronous manner compared to virgin MMTV-Neu animals. This synchrony of tumor development in the bitransgenic mice suggests that trophic maintenance of the mammary gland provides the additional events required for tumor formation and maintains the population of cells that are targeted by ErbB2/Neu for transformation. Both the synchrony of tumor appearance and the ability to characterize a window of commitment by ovariectomy/palpation studies permitted microarray analysis to evaluate changes in gene expression over a defined timeline that spans the progression from normal to preneoplastic mammary tissue. These approaches led to identification of several candidate genes whose expression changes in the mammary gland with commitment to ErbB2/Neu-induced tumorigenesis, suggesting that they may either be regulated by ErbB2/Neu and/or contribute to tumor formation.
机译：流行病学研究表明，奇偶性会增强HER2 / ErbB2 / Neu诱导的乳腺肿瘤发生。此外，最近使用过表达ErbB2 / Neu的小鼠乳腺肿瘤病毒（MMTV-Neu）小鼠的研究表明，胎次可诱导靶向ErbB2 / Neu诱导的转化的细胞群。尽管奇偶校验加速了乳腺肿瘤的发生，但多头MMTV-Neu小鼠的肿瘤发展模式仍然是随机的，这表明ErbB2 / Neu引起乳腺肿瘤还需要其他事件。此类事件是否是遗传性的，还是反映妊娠中发生的腺体动态激素控制尚不清楚。我们推测，怀孕初期或乳腺上皮细胞长期营养维持的年轻年龄可能会提供一个细胞环境，从而显着增加对ErbB2 / Neu诱导的肿瘤发生的敏感性。从3周龄开始保持妊娠或哺乳的MMTV-Neu小鼠表现出加速的肿瘤发生，但是该过程仍然是随机的，表明早期妊娠没有提供必要的肿瘤发生事件。但是，与原始MMTV-Neu动物相比，通过用促黄体激素过表达的卵巢过度刺激小鼠模型繁殖MMTV-Neu小鼠而产生的双转基因小鼠以加速，同步的方式发展了多灶性乳腺肿瘤。双转基因小鼠中肿瘤的这种同步发展表明，对乳腺的营养维持提供了肿瘤形成所需的其他事件，并维持了被ErbB2 / Neu靶向进行转化的细胞群。肿瘤外观的同步性和通过卵巢切除/触诊研究表征承诺窗口的能力都允许微阵列分析来评估跨越从正常到癌变前乳腺组织发展的定义时间轴上基因表达的变化。这些方法导致鉴定了几种候选基因，这些候选基因的表达在乳腺中发生了变化，这与ErbB2 / Neu诱导的肿瘤发生有关，这表明它们可能受ErbB2 / Neu调节和/或有助于肿瘤形成。

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