Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model.
Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model.
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DOI：
10.1038/bjc.1997.32
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发表时间：
1997
影响因子：
8.8
通讯作者：
Visakorpi T
中科院分区：
文献类型：
--
作者：
Hyytinen ER;Thalmann GN;Zhau HE;Karhu R;Kallioniemi OP;Chung LW;Visakorpi T
人类前列腺癌进展过程中的基因变化尚不完全清楚。最近，一种类似人类前列腺癌进展的实验模型系统被开发出来，该模型系统是基于一种雄激素反应性的、非致瘤性的LNCaP前列腺癌细胞系连续传代进入去势小鼠。6个不同的亚系，经过一轮、两轮或三轮体内传代后，依次获得雄激素非依赖性、致瘤性和转移能力。在这里，我们使用比较基因组杂交(CGH)和位点特异性荧光原位杂交(FISH)分析来寻找可能在该模型系统中的表型进展事件下的遗传变化。CGH在亲本LNCaP细胞系中观察到6种基因突变。衍生亚系几乎共享所有这些变化，表明共同的克隆起源，但也包含3-7个额外的遗传变化。13q12-q13染色体区域的增加以及4，6q24-qTER、20p和21q的丢失与雄激素的独立性和致瘤性相关，并与转移相关的额外变化。总之，在前列腺癌进展的实验活体模型中，基因变化的积累与肿瘤进展相关。这个模型系统中涉及的特定染色体异常可能为人类前列腺癌进展和转移相关基因的位置提供线索。
Genetic changes underlying the progression of human prostate cancer are incompletely understood. Recently, an experimental model system that resembles human prostate cancer progression was developed based on the serial passage of an androgen-responsive, non-tumorigenic LNCaP prostate cancer cell line into athymic castrated mice. Six different sublines, derived after one, two or three rounds of in vivo passage, sequentially acquired androgen independence and tumorigenicity as well as metastatic capacity. Here, we used comparative genomic hybridization (CGH) and locus-specific fluorescence in situ hybridization (FISH) analysis to search for genetic changes that may underlie the phenotypic progression events in this model system. Six genetic aberrations were seen by CGH in the parental LNCaP cell line. The derivative sublines shared virtually all these changes, indicating a common clonal origin, but also contained 3-7 additional genetic changes. Gain of the 13q12-q13 chromosomal region as well as losses of 4, 6q24-qter, 20p and 21q were associated with androgen independence and tumorigenicity with additional changes correlating with metastasis. In conclusion, an accumulation of genetic changes correlates with tumour progression in this experimental in vivo model of prostate cancer progression. It is possible that the specific chromosomal aberrations involved in this model system may provide clues to the location of genes involved in human prostate cancer progression and metastasis.