Suarez-Cabrera Cristian, Ojeda-Perez Isabel, Sanchez-Baltasar Raquel, Page Angustias, Bravo Ana, Navarro Manuel, Ramirez Angel
Translational Oncology Division, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), 28040 Madrid, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28040 Madrid, Spain.
Cancers (Basel). 2021 Nov 8;13(21):5588. doi: 10.3390/cancers13215588.
is a relatively uncharacterized gene of the Ras superfamily. It is expressed in ES cells and in the first stages of embryonic development; later on, it is silenced in the majority of cell types and tissues. Although there are several reports showing ERAS expression in tumoral cell lines and human tumor samples, it is unknown if ERAS deregulated expression is enough to drive tumor development. In this report, we have generated transgenic mice expressing ERAS in myoepithelial basal cells of the mammary gland and in basal cells of stratified epithelia. In spite of the low level of ERAS expression, these transgenic mice showed phenotypic alterations resembling overgrowth syndromes caused by the activation of the AKT-PI3K pathway. In addition, their mammary glands present developmental and functional disabilities accompanied by morphological and biochemical alterations in the myoepithelial cells. These mice suffer from tumoral transformation in the mammary glands with high incidence. These mammary tumors resemble, both histologically and by the expression of differentiation markers, malignant adenomyoepitheliomas. In sum, our results highlight the importance of silencing in adult tissues and define a truly oncogenic role for in mammary gland cells when inappropriately expressed.
是Ras超家族中一个相对未被充分表征的基因。它在胚胎干细胞和胚胎发育的最初阶段表达;后来,它在大多数细胞类型和组织中沉默。尽管有几份报告显示ERAS在肿瘤细胞系和人类肿瘤样本中有表达,但尚不清楚ERAS表达失调是否足以驱动肿瘤发展。在本报告中,我们构建了在乳腺肌上皮基底细胞和复层上皮基底细胞中表达ERAS的转基因小鼠。尽管ERAS表达水平较低,但这些转基因小鼠表现出类似于由AKT-PI3K通路激活引起的过度生长综合征的表型改变。此外,它们的乳腺存在发育和功能障碍,并伴有肌上皮细胞的形态和生化改变。这些小鼠乳腺发生肿瘤转化的发生率很高。这些乳腺肿瘤在组织学上以及通过分化标志物的表达来看,类似于恶性腺肌上皮瘤。总之,我们的结果突出了在成体组织中沉默的重要性,并确定了在乳腺细胞中不适当表达时的真正致癌作用。
Cancers (Basel). 2021-11-8
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