Isolation and characterization of LNCaP sublines differing in hormone sensitivity

Isolation and characterization of LNCaP sublines differing in hormone sensitivity
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DOI:
10.2164/jandrol.107.002675
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发表时间:
2007-09-01
影响因子:
--
通讯作者:
Hirano, Kazuyuki
Hirano, Kazuyuki
中科院分区:
其他
文献类型:
--
作者:
Iguchi, Kazuhiro;Ishii, Kenichiro;Hirano, Kazuyuki

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前列腺癌是一种具有不同程度雄激素敏感性的异质性疾病。在这项研究中,我们进行了有限稀释的人前列腺LNCaP细胞,并分离出两个亚系,LNCaP-E9和LNCaP-G4,具有不同的细胞毒性敏感性。用有限稀释法获得了两个LNCaP亚系。E9细胞的生长在雄激素的存在下,而雄激素处理的G4细胞的生长是双相的。虽然E9细胞中雄激素受体的表达水平与G4细胞中所见相似,但E9细胞中PSA mRNA和蛋白的表达显著降低。此外,基于雄激素的刺激PSA mRNA表达在E9细胞中不如G4细胞敏感。E9和G4细胞内锌水平没有差异,但ZnT 3 mRNA表达在E9细胞中显着较高。当细胞被移植到肾包膜下时,具有管腔的CD 31阳性血管的数量比G4肿瘤中的高约2.5倍。LNCaP-E9细胞显示出比LNCaP-G4细胞更低的雄激素敏感性。E9和G4细胞将有助于了解难治性前列腺癌的生物学。
Prostate cancer is a heterogeneous disease with varying degrees of androgen sensitivity. In this study, we performed a limiting dilution of human prostate LNCaP cells, and isolated two sublines, LNCaP-E9 and LNCaP-G4, with differential hormone-sensitivity. Two LNCaP sublines were obtained by the limiting dilution method. The growth of E9 cells was decreased in the presence of androgens, while that of androgen-treated G4 cells was biphasic. Although the androgen receptor expression level in E9 cells was similar to that seen in G4 cells, the expression of PSA mRNA and protein was significantly lower in the E9 cells. Moreover, the androgen-based stimulation of PSA mRNA expression was less sensitive in E9 cells than G4 cells. Intracellular zinc level did not differ between E9 and G4 cells, but ZnT3 mRNA expression was significantly higher in the E9 cells. When the cells were grafted at the subrenal capsule, the number of CD31-positive vessels with a lumen was approximately 2.5 times higher than that in G4 tumors. LNCaP-E9 cells show lower androgen sensitivity than LNCaP-G4 cells. E9 and G4 cells would be helpful for understanding the biology of hormone-refractory prostate cancer.