CXCL12 activates a robust transcriptional response in human prostate epithelial cells
CXCL12 activates a robust transcriptional response in human prostate epithelial cells
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DOI：
10.1074/jbc.m700440200
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发表时间：
2007-09-14
影响因子：
4.8
通讯作者：
Macoska, Jill A.
中科院分区：
文献类型：
--
作者：
Begley, Lesa A.;MacDonald, James W.;Macoska, Jill A.
CXCL12 是一种 CXC 型趋化因子，在造血、发育和免疫系统组织中发挥重要作用，并支持多种正常或恶性细胞类型的存活或生长。我们实验室最近发现CXCL12是由老化的基质成纤维细胞分泌的，是特异性刺激前列腺上皮细胞增殖的主要旁分泌因子。目前的研究表明，这种 CXCL12 介导的增殖反应可能是 ERK 依赖性的，也可能是 ERK 独立的。此外，CXCL12 在前列腺上皮细胞中启动了先前未定义且复杂的全局转录反应。这种CXCL12介导的转录反应直接刺激编码参与促进细胞增殖和细胞周期进展、肿瘤转移和细胞运动的蛋白质的基因的表达，并直接抑制编码参与细胞间粘附和抗凋亡的蛋白质的基因的转录。因此，CXCL12可能在组织微环境老化的良性增殖性疾病的病因学中发挥重要作用。
CXCL12 is a CXC-type chemokine that plays important roles in hematopoiesis, development, and organization of the immune system and supports the survival or growth of a variety of normal or malignant cell types. Our laboratory recently showed that CXCL12 is secreted by aging stromal fibroblast cells and is a major paracrine factor that specifically stimulates the proliferation of prostate epithelial cells. The current study shows that this CXCL12-mediated proliferative response may be either ERK-dependent or ERK-independent. Moreover, CXCL12 initiates a previously undefined and complex global transcriptional response in prostate epithelial cells. This CXCL12-mediated transcriptional response directly stimulates the expression of genes encoding proteins that are involved in the promotion of cellular proliferation and progression through the cell cycle, tumor metastasis, and cellular motility, and directly represses the transcription of genes encoding proteins involved in cell-cell adhesion and resistance to apoptosis. Thus, CXCL12 may play a major role in the etiology of benign proliferative disease in the context of an aging tissue microenvironment.