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Restriction of neuroblastoma to the prostate gland in transgenic mice.

机译:转基因小鼠中神经母细胞瘤对前列腺的限制。

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Male transgenic mice that carry a construct containing 5'-flanking sequences of the gp91-phox gene linked to the early region of the simian virus 40 (SV40) genome reproducibly develop tumors arising from the prostate gland. As gp91-phox is expressed exclusively in terminally differentiating hematopoietic cells of the myelomonocytic lineage, the induction of tumors arising from the prostate gland was unexpected. These lesions appear to be due to a novel transcription signal that was generated during the construction of the transgene. Surprisingly, the histopathological and biochemical properties of the tumor are diagnostic of neuroblastoma rather than of adenocarcinoma of the prostate gland. Tumors produce SV40 T antigen and isoforms of neural cell adhesion molecule characteristic of neuronal cells, and they occur in a testosterone-independent manner. Microscopic examination of prostate glands from young transgenic mice reveals the presence of small lesions arising outside of the prostate gland epithelium, which is consistent with the diagnosis of neuroblastoma and further distinguishes this tumor from prostatic adenocarcinoma. Prostate gland tumors occur in all male animals of susceptible lines carrying the gp91-phox promoter/SV40 early-region transgene. However, variability in the time at which gross tumors appear and the presence of cells expressing T antigen prior to tumorigenesis suggest that somatic events in addition to T-antigen production are required for the development of a malignancy. The extraordinary restriction of the site of tumorigenesis in these animals indicates the presence in the prostate gland of a novel, tissue-specific neuroectodermal cell of origin. These transgenic animals provide a model system for the study of neuroectodermal malignancies.
机译:携带含有与猿猴病毒40(SV40)基因组的早期区域连接的gp91-phox基因5'侧翼序列的构建体的雄性转基因小鼠可繁殖性地发展为前列腺癌。由于gp91-phox仅在骨髓单核细胞谱系的终末分化造血细胞中表达,因此诱导前列腺腺肿瘤是出乎意料的。这些损伤似乎是由于在转基因的构建过程中产生的新型转录信号所致。令人惊讶的是,肿瘤的组织病理学和生化特性可诊断成神经母细胞瘤,而不是前列腺腺癌。肿瘤产生SV40 T抗原和神经元细胞特有的神经细胞粘附分子同工型,并以不依赖睾丸激素的方式发生。显微镜检查了来自年轻转基因小鼠的前列腺,发现存在在前列腺上皮外部出现的小病变,这与神经母细胞瘤的诊断是一致的,并且进一步将该肿瘤与前列腺腺癌区分开来。前列腺癌出现在所有携带gp91-phox启动子/ SV40早期区域转基因的易感系雄性动物中。然而,发生肿瘤前的时间变化和肿瘤发生前表达T抗原的细胞的存在表明,恶性肿瘤的发生还需要除T抗原产生以外的体细胞事件。这些动物中肿瘤发生部位的特殊限制表明前列腺中存在一种新颖的组织特异性神经外胚层细胞。这些转基因动物为研究神经外胚层恶性肿瘤提供了模型系统。

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