MMTV-EGF receptor transgene promotes preneoplastic conversion of multiple steroid hormone-responsive tissues.
MMTV-EGF receptor transgene promotes preneoplastic conversion of multiple steroid hormone-responsive tissues.
复制标题
MMTV-EGF 受体转基因促进多种类固醇激素反应组织的癌前转化。
DOI：
10.1002/jcb.21591
复制
发表时间：
2008
影响因子：
4
通讯作者：
Parsons,SarahJ
中科院分区：
文献类型：
--
作者：
Marozkina,NadzeyaV;Stiefel,StevenM;FriersonJr,HenryF;Parsons,SarahJ
对人类生殖系统肿瘤和患者源性细胞系的相关分析表明，EGF的过度表达有助于致癌表型。然而，目前还不清楚在疾病的哪个阶段EGFR的过度表达是最关键的。为了评估其作为生殖组织肿瘤发生引发剂的作用，用小鼠乳腺肿瘤病毒（MMTV）调节的人EGFR过表达衍生转基因小鼠。尽管观察到EGFR在肿瘤反应组织中的表达升高，但在2年内仅1只EGFR转基因小鼠发生可见肿瘤。然而，在同一时间监测的12只雌性动物中，在55%的检查动物的乳腺、89%的子宫或子宫角以及100%的卵巢或输卵管中发现增生、肥大或轻微发育不良。雄性转基因动物或年龄匹配的正常小鼠的生殖组织均未显示这些变化。这些结果揭示了EGFR在卵巢癌和子宫癌的起始中的作用，并支持了先前在乳腺癌中的研究，即受体可以以显著但递增的方式促进肿瘤过程。J.细胞。生物化学103：2010-2018，2008。© 2007 Wiley利斯公司
Correlative analyses of tumors and patient‐derived cell lines of the human reproductive system suggest that overexpression of EGF contributes to the oncogenic phenotype. However, it is unclear at what stage in disease overexpression of the EGFR is most critical. To assess its role as an initiator of reproductive tissue tumor development, transgenic mice were derived with mouse mammary tumor virus (MMTV)‐regulated overexpression of the human EGFR. Although elevated expression of the EGFR in hormonally responsive tissues was observed, only one EGFR transgenic mouse developed a visible tumor over a 2‐year period. However, of 12 females monitored over the same time, hyperplasia, hypertrophy, or slight dysplasia was found in mammary glands of 55% of the animals examined, in the uterus or uterine horn of 89%, and in ovaries or oviducts of 100%. None of the reproductive tissues of the male transgenic animals or age‐matched, normal mice displayed these changes. These results revealed a role for the EGFR in the initiation of ovarian and uterine cancer and supported previous studies in breast cancer that the receptor can contribute to the neoplastic process in a significant albeit incremental way. J. Cell. Biochem. 103: 2010–2018, 2008. © 2007 Wiley‐Liss, Inc.