2016年6月28日讯/生物谷BIOON/–最近,一项发表在国际杂志Science上的研究论文中,来自哥伦比亚大学医学中心的研究人员通过研究发现,单一基因的表达就可以将骨盆精囊中的内衬细胞转化成为前列腺细胞,这项研究或可帮助深入理解控制前列腺组织和精囊发育背后的分子机制,同时还可以帮助科学家们揭示为何癌症通常多发于前列腺而很少在精囊组织中发生。
此前研究中,研究者Aditya·Dutta等人通过研究发现,Nkx3.1基因的缺失会损伤小鼠前列腺的分化;为了深入研究Nkx3.1基因,首先研究人员证实,前列腺细胞中Nkx3.1基因的缺失会导致和前列腺分化的一系列基因表达水平的降低。
随后研究者利用表达Nkx3.1基因的病毒感染精囊上皮细胞,结果发现,诱导该基因表达会促进精囊上皮细胞转化成为前列腺样状态的细胞,而这种转化后的细胞在结构、遗传标记及组织学表现上均同前列腺细胞类似。
研究者认为,对人类前列腺细胞进行深入研究,或许会帮助鉴别出参与组织再组装更新过程中所涉及的多种调节网络组分,其中就包括特殊的组蛋白修饰酶类;后期研究人员还将继续通过更为深入的研究来理解前列腺癌组织特异性的奥秘,或为开发治疗前列腺癌的新型疗法提供一定思路和希望。(基因宝jiyinbao.com)
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Identification of an NKX3.1-G9a-UTY transcriptional regulatory network that controls prostate differentiation
Aditya Dutta1,*, Clémentine Le Magnen1,*, Antonina Mitrofanova2,†, Xuesong Ouyang3,‡, Andrea Califano4, Cory Abate-Shen5,§
The NKX3.1 homeobox gene plays essential roles in prostate differentiation and prostate cancer. We show that loss of function of Nkx3.1 in mouse prostate results in down-regulation of genes that are essential for prostate differentiation, as well as up-regulation of genes that are not normally expressed in prostate. Conversely, gain of function of Nkx3.1 in an otherwise fully differentiated nonprostatic mouse epithelium (seminal vesicle) is sufficient for respecification to prostate in renal grafts in vivo. In human prostate cells, these activities require the interaction of NKX3.1 with the G9a histone methyltransferase via the homeodomain and are mediated by activation of target genes such as UTY (KDM6c), the male-specific paralog of UTX (KDM6a). We propose that an NKX3.1-G9a-UTY transcriptional regulatory network is essential for prostate differentiation, and we speculate that disruption of such a network predisposes to prostate cancer.