ERAS, a Member of the Ras Superfamily, Acts as an Oncoprotein in the Mammary Gland

<i>ERAS</i> 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...

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Autores principales: Cristian Suarez-Cabrera, Isabel Ojeda-Perez, Raquel Sanchez-Baltasar, Angustias Page, Ana Bravo, Manuel Navarro, Angel Ramirez
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/164c4c4eca474bfaa7a6362328bc4e40
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Sumario:<i>ERAS</i> 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 <i>ERAS</i> silencing in adult tissues and define a truly oncogenic role for <i>ERAS</i> in mammary gland cells when inappropriately expressed.