Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Cell Prolif. 2011 Aug;44(4):311-9. doi: 10.1111/j.1365-2184.2011.00757.x. Epub 2011 Jun 6.
The focus of this study was to determine the dedicator of cytokinesis 2 (DOCK2), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase-1 (JNK) and Akt signals involved in CXCL13-mediated prostate cancer (PCa) cell invasion and proliferation.
Androgen-sensitive (LNCaP), hormone-refractory (PC3) cells and normal cells (RWPE-1) were used to determine CXCL13-mediated PCa cell invasion and proliferation. Immuno-blotting, fast activated cell-based (FACE) ELISA, caspase activity, cell invasion and proliferation assays were performed to ascertain some of the signalling events involved in PCa cell proliferation and invasion.
Unlike androgen-sensitive LNCaP cells, we report for the first time that the hormone-refractory cell line, PC3, expresses DOCK2. CXCL13-mediated LNCaP and PC3 cell invasion was regulated by Akt and ERK1/2 activation in a DOCK2-independent fashion. CXCL13 also promoted LNCaP cell proliferation in a JNK-dependent fashion even in the absence of DOCK2. In contrast, CXCL13 induced PC3 cell proliferation through JNK activation, which required DOCK2.
Our results show CXCL13-mediated PCa cell invasion requires Akt and ERK1/2 activation and suggests a new role for DOCK2 in proliferation of hormone-refractory CXCR5-positive PCa cells.
本研究的重点是确定细胞分裂的定向因子 2（DOCK2）、细胞外信号调节激酶 1/2（ERK1/2）、c-Jun N 端激酶-1（JNK）和 Akt 信号在 CXCL13 介导的前列腺癌（PCa）细胞侵袭和增殖中的作用。
使用雄激素敏感（LNCaP）、激素抵抗（PC3）细胞和正常细胞（RWPE-1）来确定 CXCL13 介导的 PCa 细胞侵袭和增殖。进行免疫印迹、快速激活细胞基于（FACE）ELISA、半胱氨酸天冬氨酸蛋白酶活性、细胞侵袭和增殖测定，以确定参与 PCa 细胞增殖和侵袭的部分信号事件。
与雄激素敏感的 LNCaP 细胞不同，我们首次报道激素抵抗细胞系 PC3 表达 DOCK2。CXCL13 介导的 LNCaP 和 PC3 细胞侵袭受 Akt 和 ERK1/2 激活调节，与 DOCK2 无关。CXCL13 还以依赖于 JNK 的方式促进 LNCaP 细胞增殖，即使没有 DOCK2 也是如此。相反，CXCL13 通过 JNK 激活诱导 PC3 细胞增殖，这需要 DOCK2。
我们的研究结果表明，CXCL13 介导的 PCa 细胞侵袭需要 Akt 和 ERK1/2 激活，并提示 DOCK2 在激素抵抗的 CXCR5 阳性 PCa 细胞增殖中发挥新的作用。
