Shain S A, Huot R I, Gorelic L S, Smith G C
Cancer Res. 1984 May;44(5):2033-42.
We used three heterogeneous parental cultures of LSC-AXC rat prostate cancer cells: LSC-AXC-C/O, cells maintained on culture medium; LSC-AXC-D/O, cells maintained on culture medium containing 10(-7) M 5 alpha-dihydrotestosterone; and LSC-AXC-T/O, cells maintained on culture medium containing 10(-7) M testosterone, to isolate clonally derived cell lines. Eleven of 15 clonal cell lines were tumorigenic when inoculated into intact male AXC rats. Eight tumorigenic clonal cell lines were selected for further evaluation, and all were found to possess features characteristic of secretory epithelium, as judged by light and electron microscopy. All parental cell lines and the eight selected clonal cell lines contained cytoplasmic and nuclear androgen receptors. Total receptor content was 131 +/- 61 (S.D.), 43 +/- 32, and 274 +/- 96 fmol/100 micrograms of DNA, respectively, for C-, D-, and T-cells. The differences were significant (p less than 0.05). Androgen receptor content of young mature or senescent AXC rat ventral prostate, respectively, is 518 +/- 58 and 266 +/- 40 fmol/100 micrograms of DNA. Since chromosomal analysis established that LSC-AXC prostate cancer cells are hypotriploid, androgen receptor content per cell in C- and T-cells is indicated to be either greater than or equal to that of senescent AXC rat ventral prostate, the tissue in which the original adenocarcinoma arose. Parental and clonal cell lines contained 5 alpha-reductase activity. There were significant differences (p less than 0.05) in both total reductase activity and metabolite distribution. Consequently, the intracellular content of testosterone metabolites was cell line specific. All characterized cell lines contained a higher concentration (p less than 0.05) of APase activity than did young mature or senescent AXC rat ventral prostate. In 6 of 11 cell lines, prostate-secretory APase concentration exceeded (p less than 0.05) that of AXC rat ventral prostate. However, the relative content of secretory APase compared to total APase in carcinoma cells consistently was less (p less than 0.05) than that of AXC rat ventral prostate. These studies document the establishment of clonal AXC rat prostate adenocarcinoma cell lines which have retained important morphological and phenotypic markers characteristic of differentiated prostate epithelium. Since these cells are tumorigenic and represent a spectrum of retained differentiated phenotypic markers, they should be particularly useful for in vivo and in vitro studies of hormonal regulation of prostate cancer cell behavior.
我们使用了三种异质性的LSC - AXC大鼠前列腺癌细胞系亲代培养物：LSC - AXC - C/O，在培养基上培养的细胞；LSC - AXC - D/O，在含有10(-7) M 5α - 二氢睾酮的培养基上培养的细胞；以及LSC - AXC - T/O，在含有10(-7) M睾酮的培养基上培养的细胞，以分离克隆衍生的细胞系。将15个克隆细胞系中的11个接种到完整的雄性AXC大鼠体内时具有致瘤性。选择了8个具有致瘤性的克隆细胞系进行进一步评估，通过光镜和电镜判断，发现它们均具有分泌上皮的特征。所有亲代细胞系和8个选定的克隆细胞系均含有细胞质和细胞核雄激素受体。C细胞、D细胞和T细胞的总受体含量分别为131±61（标准差）、43±32和274±96 fmol/100微克DNA。差异具有统计学意义（p<0.05）。年轻成熟或衰老的AXC大鼠腹侧前列腺的雄激素受体含量分别为518±58和266±40 fmol/100微克DNA。由于染色体分析确定LSC - AXC前列腺癌细胞为亚三倍体，表明C细胞和T细胞中每个细胞的雄激素受体含量大于或等于衰老的AXC大鼠腹侧前列腺（原始腺癌发生的组织）中的含量。亲代和克隆细胞系均具有5α - 还原酶活性。总还原酶活性和代谢产物分布均存在显著差异（p<0.05）。因此，睾酮代谢产物的细胞内含量具有细胞系特异性。所有已鉴定的细胞系中碱性磷酸酶（APase）活性浓度均高于年轻成熟或衰老的AXC大鼠腹侧前列腺（p<0.05）。在11个细胞系中的6个中，前列腺分泌性APase浓度超过了AXC大鼠腹侧前列腺（p<0.05）。然而，癌细胞中分泌性APase与总APase的相对含量始终低于AXC大鼠腹侧前列腺（p<0.05）。这些研究记录了克隆的AXC大鼠前列腺腺癌细胞系的建立，这些细胞系保留了分化前列腺上皮的重要形态和表型标记。由于这些细胞具有致瘤性且代表了一系列保留的分化表型标记，它们对于前列腺癌细胞行为的激素调节的体内和体外研究应该特别有用。
