Enhanced sensitivity to androgen withdrawal due to overexpression of interleukin-6 in androgen-dependent human prostate cancer LNCaP cells.
Enhanced sensitivity to androgen withdrawal due to overexpression of interleukin-6 in androgen-dependent human prostate cancer LNCaP cells.
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DOI：
10.1038/sj.bjc.6605358
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发表时间：
2009-11-17
影响因子：
8.8
通讯作者：
Fujisawa, M.
中科院分区：
文献类型：
--
作者：
Terakawa, T.;Miyake, H.;Furukawa, J.;Ettinger, S. L.;Gleave, M. E.;Fujisawa, M.
关键词：
本研究的目的是探讨白细胞介素-6（IL-6）在雄激素依赖性前列腺癌LNCaP细胞中过表达对其表型的影响。我们通过引入含有IL-6 cDNA的表达载体，建立了IL-6过表达LNCaP（LNCaP/IL-6）。将LNCaP/IL-6中表型的变化与仅用对照载体转染的LNCaP（LNCaP/Co）中的表型变化进行比较。在体外，在雄激素剥夺条件下，LNCaP/IL-6的生长显著劣于LNCaP/Co。类似地，裸鼠中的LNCaP/IL-6肿瘤在去势后迅速消退;然而，LNCaP/Co肿瘤生长在去势后被短暂抑制，然后持续加速。与LNCaP/Co组相比，LNCaP/IL-6组雄激素撤除后磷酸化p44/42丝裂原活化蛋白激酶（MAPK）和Akt的表达水平显著上调;然而，与LNCaP/Co相比，用MAPK或Akt信号传导途径的特异性抑制剂的额外处理显著抑制LNCaP/IL-6的生长。此外，基因芯片分析表明，雄激素剥夺导致LNCaP/Co和LNCaP/IL-6之间参与生长、肿瘤和肿瘤发生的基因的差异表达。LNCaP细胞以自分泌方式过度分泌IL-6可能在雄激素剥夺条件下对它们的生长和雄激素非依赖性表型的获得具有抑制作用。
The objective of this study was to investigate the effects of interleukin-6 (IL-6) overexpression in androgen-dependent prostate cancer LNCaP cells on their phenotype under an androgen-deprived condition. We established IL-6-overexpressing LNCaP (LNCaP/IL-6) by introducing the expression vector containing IL-6 cDNA. Changes in the phenotype in LNCaP/IL-6 were compared with that in LNCaP transfected with control vector alone (LNCaP/Co). In vitro, the growth of LNCaP/IL-6 was significantly inferior to that of LNCaP/Co under an androgen-deprived condition. Similarly, LNCaP/IL-6 tumour in nude mice rapidly regressed after castration; however, LNCaP/Co tumour growth was transiently inhibited after castration and then continuously accelerated. After androgen withdrawal, expression levels of phosphorylated p44/42 mitogen-activated protein kinase (MAPK) and Akt in LNCaP/IL-6 were markedly upregulated compared with those in LNCaP/Co; however, additional treatment with specific inhibitor of the MAPK or Akt signalling pathway significantly inhibited the growth of LNCaP/IL-6 compared with that of LNCaP/Co. Furthermore, gene microarray analyses showed that androgen deprivation resulted in differential expression of genes involved in growth, apoptotsis and tumorigenesis between LNCaP/Co and LNCaP/IL-6. Excessive secretion of IL-6 by LNCaP cells in an autocrine manner may have a suppressive function in their growth and acquisition of androgen-independent phenotype under an androgen-deprived condition.
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