Garabedian E M, Humphrey P A, Gordon J I
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15382-7. doi: 10.1073/pnas.95.26.15382.
A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides -6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progresses rapidly to local invasion. Metastases to lymph nodes, liver, lung, and bone are common by 6 months. Tumorigenesis is not dependent on androgens. This model indicates that the neuroendocrine cell lineage of the prostate is exquisitely sensitive to transformation and provides insights about the significance of neuroendocrine differentiation in human prostate cancer.
已开发出一种转移性前列腺癌的转基因小鼠模型，该模型在多个谱系中具有100%的穿透率。小鼠隐窝防御素-2基因的核苷酸-6500至+34用于将猿猴病毒40 T抗原定向表达至FVB/N小鼠前列腺所有叶中的一部分神经内分泌细胞。转基因表达在7至8周龄时开始，并在一周内导致前列腺上皮内瘤变的发生。前列腺上皮内瘤变迅速发展为局部浸润。到6个月时，转移至淋巴结、肝脏、肺和骨骼很常见。肿瘤发生不依赖雄激素。该模型表明前列腺的神经内分泌细胞谱系对转化极为敏感，并为人类前列腺癌中神经内分泌分化的意义提供了见解。
