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Epithelial ovarian cancer: focus on genetics and animal models.

机译：上皮性卵巢癌：关注遗传学和动物模型。

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摘要

Despite rapid advances in understanding ovarian cancer etiology, epithelial ovarian cancer remains the most lethal form of gynecologic cancers in the United States. The four morphologically-defined epithelial ovarian cancer subtypes-serous, endometrioid, mucinous, and clear cell carcinomas--are generally believed to originate from ovarian epithelial cells. Although it remains unclear how this single cell layer gives rise to morphologically distinct cancers, it has been suggested that early genetic events may direct the differentiation of ovarian epithelial cells. A number of genetic alterations are frequently encountered during ovarian tumorigenesis, including oncogenic activities of KRAS, BRAF and AKT, and silencing mutations of TP53, RB and PTEN. However, knowledge about how these genetic elements are coordinated during ovarian cancer initiation and progression is very limited. The establishment of cell-culture systems and rodent-based models has made big strides towards a better understanding of thegenetic bases of human epithelial ovarian tumorigenesis. More importantly, the rise of genetically-engineered rodent and human models, particularly in the past five years, has provided key insight in the role of specific genes during ovarian tumorigenesis. In this review, we offer a comprehensive coverage of currently-available in vitro and in vivo models of human epithelial ovarian cancer, focusing on latest updates of genetically-modified rodent and human models and the valuable information conveyed by them.
机译：尽管在了解卵巢癌病因方面取得了迅速的进步，但上皮性卵巢癌仍然是美国妇科癌症中最致命的形式。通常认为四种形态上定义的上皮性卵巢癌亚型-浆液性，子宫内膜样，粘液性和透明细胞癌-均起源于卵巢上皮细胞。尽管尚不清楚该单细胞层如何引起形态上不同的癌症，但已表明早期遗传事件可能指导卵巢上皮细胞的分化。卵巢肿瘤发生过程中经常遇到许多遗传改变，包括KRAS，BRAF和AKT的致癌活性以及TP53，RB和PTEN的沉默突变。但是，关于这些遗传元素如何在卵巢癌发生和发展过程中协调的知识非常有限。细胞培养系统和基于啮齿动物的模型的建立已朝着更好地了解人类上皮性卵巢肿瘤发生的遗传基础迈出了一大步。更重要的是，基因工程啮齿动物模型和人类模型的兴起，尤其是在过去的五年中，为特定基因在卵巢肿瘤发生中的作用提供了重要的见识。在这篇综述中，我们提供了人类上皮性卵巢癌目前可用的体外和体内模型的全面报道，重点是转基因啮齿动物和人类模型的最新更新以及它们所传达的宝贵信息。

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