雌激素受体阳性乳腺癌肿瘤发育新靶点

　　乳房等器官或肿瘤的发育和生长，受到互相协调的细胞增殖分化程序控制。其中，转录因子驱动乳房发育和功能的信号逐级传递网络已被广泛研究。信使核糖核酸（mRNA）下游3'端非翻译区包含顺式调节元件的组合集群可以通过关联RNA结合蛋白对蛋白质合成的转录RNA特异调节作用进行定义。其中，RNA结合细胞质多腺苷酸化元件结合蛋白CPEB家族共同调节了大约30%的基因组mRNA翻译。不过，转录后基因表达重编程的作用机制尚不明确。

　　2020年5月15日，美国科学促进会《科学》旗下《科学进展》在线发表西班牙巴塞罗那科学技术学院、加泰罗尼亚高等研究院、巴塞罗那癌症网络生物医学研究中心、中国台湾中央研究院生物医学科学研究所的研究报告，分析了CPEB家族对乳房发育和雌激素受体阳性乳腺癌肿瘤发育的作用机制。

　　该研究发现，CPEB家族二号人物——CPEB2通过控制雌激素受体/孕激素受体对DNA转录产生RNA进行调节，从而控制蛋白质表达，是激素信号传导整合必需的。此外，CPEB2对于雌激素受体阳性乳腺肿瘤发育至关重要。

　　因此，该研究结果表明，乳房形态发生和雌激素受体阳性乳腺癌肿瘤发生过程存在以前未知的基因表达调节机制，协调了序贯转录和转录后基因表达调节作用，CPEB2有望成为雌激素受体阳性乳腺癌的新靶点。

Sci Adv. 2020 May 15;6(20):eaax3868.

The RNA binding protein CPEB2 regulates hormone sensing in mammary gland development and luminal breast cancer.

Rosa Pascual, Judit Martín, Fernando Salvador, Oscar Reina, Veronica Chanes, Alba Millanes-Romero, Clara Suner, Gonzalo Fernández-Miranda, Anna Bartomeu, Yi-Shuian Huang, Roger R. Gomis, Raúl Méndez.

The Barcelona Institute of Science and Technology, Barcelona, Spain; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Institució Catalana de Recerca i Estudis Avancats, Barcelona, Spain; Centro de Investigación Biomédica en Red de Cáncer, Barcelona, Spain.

Organogenesis is directed by coordinated cell proliferation and differentiation programs. The hierarchical networks of transcription factors driving mammary gland development and function have been widely studied. However, the contribution of posttranscriptional gene expression reprogramming remains largely unexplored. The 3' untranslated regions of messenger RNAs (mRNAs) contain combinatorial ensembles of cis-regulatory elements that define transcript-specific regulation of protein synthesis through their cognate RNA binding proteins. We analyze the contribution of the RNA binding cytoplasmic polyadenylation element-binding (CPEB) protein family, which collectively regulate mRNA translation for about 30% of the genome. We find that CPEB2 is required for the integration of hormonal signaling by controlling the protein expression from a subset of ER/PR- regulated transcripts. Furthermore, CPEB2 is critical for the development of ER-positive breast tumors. This work uncovers a previously unknown gene expression regulation level in breast morphogenesis and tumorigenesis, coordinating sequential transcriptional and posttranscriptional layers of gene expression regulation.

DOI: 10.1126/sciadv.aax3868