Bae V L, Jackson-Cook C K, Maygarden S J, Plymate S R, Chen J, Ware J L
Department of Pathology, Medical College of Virginia Campus, Richmond 23298, USA.
Prostate. 1998 Mar 1;34(4):275-82. doi: 10.1002/(sici)1097-0045(19980301)34:4<275::aid-pros5>3.0.co;2-g.
The available human prostate cancer cell lines that are metastatic in athymic nude mice all have complex, highly aneuploid karyotypes. Other prostatic cells immortalized by transforming genes of SV40 or HPV and converted to tumorigenicity by additional genetic manipulation are not reported to be metastatic.
Tumorigenic sublines of human prostate epithelial cells previously immortalized by transfection with the SV40T antigen gene were obtained by sequential passage in male athymic nude mice. These sublines were evaluated histopathologically for tumorigenicity and metastasis in athymic nude mice after subcutaneous, intraperitoneal, and intraprostatic injection. Each subline was characterized by standard (GTG-banding) cytogenetic and FISH analysis, and RNase protection assays for androgen receptor expression.
Two sublines produced metastases in lungs and the diaphragm of most mice after either intraprostatic or intraperitoneal injection. The M2205 subline formed large local tumors after intraprostatic injection. Cytogenetic aberrations present in the metastatic sublines, but not in the tumorigenic, nonmetastatic lines or the parental P69SV40T line, included dup(11)(q14q22), der(16) t (16;19) (q24;q13.1), which resulted in the loss of the short arm and proximal long arm of chromosome 19 (19q13.1-->19pter), and loss of the Y chromosome. None of the sublines expressed the androgen receptor.
These cytogenetically defined, SV40T-immortalized human prostate epithelial cell lines, with distinct biological behaviors in vivo, provide additional tools for the genetic analysis of the emergence of metastatic capacity.
现有的在无胸腺裸鼠中具有转移能力的人前列腺癌细胞系都具有复杂的、高度非整倍体的核型。其他通过SV40或HPV的转化基因永生化并通过额外的基因操作转化为致瘤性的前列腺细胞尚未见有转移的报道。
通过在雄性无胸腺裸鼠中连续传代，获得了先前用SV40T抗原基因转染永生化的人前列腺上皮细胞的致瘤亚系。在皮下、腹腔内和前列腺内注射后，对这些亚系在无胸腺裸鼠中的致瘤性和转移情况进行组织病理学评估。每个亚系通过标准（GTG显带）细胞遗传学和荧光原位杂交分析以及雄激素受体表达的核糖核酸酶保护试验进行表征。
两个亚系在前列腺内或腹腔内注射后，在大多数小鼠的肺和横膈膜产生了转移。M2205亚系在前列腺内注射后形成了大的局部肿瘤。转移亚系中存在的细胞遗传学异常，但在致瘤性、非转移性系或亲本P69SV40T系中不存在，包括dup(11)(q14q22)、der(16)t(16;19)(q24;q13.1)，这导致19号染色体短臂和近端长臂丢失（19q13.1→19pter）以及Y染色体丢失。没有一个亚系表达雄激素受体。
这些细胞遗传学定义的、SV40T永生化的人前列腺上皮细胞系在体内具有独特的生物学行为，为转移能力出现的遗传分析提供了额外的工具。
