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Transcription regulators are transiently expressed during the prostate gland adaptation to the hypoandrogenic environment.
Histology and Histopathology ( IF 2.5 ) Pub Date : 2019-03-26 , DOI: 10.14670/hh-18-105
Umar Nishan 1 , Rafaela Rosa-Ribeiro 1 , Carlos Lenz Cesar 2, 3 , Hernandes F Carvalho 1, 3
Affiliation  

The high incidence of prostatic diseases, including malignant tumors, makes the understanding of prostate biology very important. Androgen deprivation, blockade by orchiectomy, or chemical castration causes prostate and tumor shrinkage. The gene networks involved in a cell type-specific fashion are rather unknown. This work was undertaken to identify genes with annotated function in transcription regulation that might define transitions in gene expression. A total of 15 potential regulatory genes were identified. Validation by qRT-PCR showed that Zfp703 and Arid1a exhibit expression maxima at day 1; Ash2l, Nelf, Pbx3, Eya2 at day 4; Dmrt2 at day 5 and Lbh and Sox1 at day 7 after castration. Using immunohistochemistry, we further determined that PBX3 was found in both stromal and epithelial cells, whereas ARID1A and NELF were restricted to the epithelium, and DMRT2 and EYA2 were exclusively found in the stroma. Though the proteins ZFP703 and ASH2l were not found in any experimental condition, their mRNAs were located by in situ hybridization in both epithelium and stroma. In conclusion, androgen deprivation triggers the expression of temporally regulated gene sets in both epithelial and stromal cells. These gene subsets will help establish the regulatory gene expression programs orchestrating the castration-induced remodeling of the prostate gland, and represent putative targets to increase the efficacy of androgen-deprivation to induce epithelial (and cancer) cell death.

中文翻译:

转录调节剂在前列腺适应低雄激素环境中瞬时表达。

包括恶性肿瘤在内的前列腺疾病的高发率使得对前列腺生物学的理解非常重要。雄激素缺乏,睾丸切除术阻滞或化学去势会导致前列腺和肿瘤缩小。涉及细胞类型特异性方式的基因网络是相当未知的。进行这项工作以鉴定在转录调控中具有注释功能的基因,该基因可能定义基因表达的转变。总共鉴定出15个潜在的调控基因。qRT-PCR验证显示Zfp703和Arid1a在第1天表现出最大表达;第4天的Ash2l,Nelf,Pbx3,Eya2;去势后第5天为Dmrt2,第7天为Lbh和Sox1。使用免疫组织化学,我们进一步确定在基质细胞和上皮细胞中均发现了PBX3,而ARID1A和NELF仅限于上皮,而DMRT2和EYA2仅在基质中发现。尽管在任何实验条件下均未发现蛋白ZFP703和ASH21,但它们的mRNA通过原位杂交定位在上皮和基质中。总之,雄激素剥夺触发了上皮和基质细胞中时间调控基因集的表达。这些基因子集将帮助建立调节基因表达程序,以协调去势诱导的前列腺重塑,并代表推定的靶点,以增加雄激素剥夺诱导上皮(和癌细胞)死亡的功效。它们的mRNA通过原位杂交定位在上皮和基质中。总之,雄激素剥夺触发了上皮和基质细胞中时间调控基因集的表达。这些基因子集将帮助建立调节基因表达程序,以协调去势诱导的前列腺重塑,并代表推定的靶点,以增加雄激素剥夺诱导上皮(和癌细胞)死亡的功效。它们的mRNA通过原位杂交定位在上皮和基质中。总之,雄激素剥夺触发了上皮和基质细胞中时间调控基因集的表达。这些基因子集将帮助建立调节基因表达程序,以协调去势诱导的前列腺重塑,并代表推定的靶点,以增加雄激素剥夺诱导上皮(和癌细胞)死亡的功效。
更新日期:2020-08-21
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