Ling Ming-Tat, Wang Xianghong, Ouyang Xue-Song, Lee Terence K W, Fan Tian-Yong, Xu Kexin, Tsao Sai-Wah, Wong Y C
Cancer Biology Laboratory, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
Oncogene. 2002 Dec 5;21(55):8498-505. doi: 10.1038/sj.onc.1206007.
The helix-loop-helix protein Id-1 has been suggested to play a positive role in cell proliferation and tumorigenesis of many types of human cancers. However, little is known about the molecular mechanism involved in the function of Id-1. In this study, using four stable Id-1 transfectant clones, we investigated the involvement of MAPK signaling pathway in the Id-1 induced serum independent prostate cancer cell growth. Our results demonstrated that both transient and stable ectopic Id-1 expression in prostate cancer LNCaP cells led to activation of the Raf/MEK1/2 signaling pathway. In addition, inhibition of MEK1/2 phosphorylation by one of its inhibitors, PD098059, resulted in the decreased cell cycle S phase fraction and cell growth rate, suggesting that activation of MAPK signaling pathway is essential for Id-1 induced prostate cancer cell proliferation. Furthermore, treatment with antisense oligonucleotide complementary to Id-1 mRNA in PC-3 and DU145 cells resulted in a decreased Id-1 expression which was accompanied by decreased Egr-1 protein. Our results suggest for the first time that the function of Id-1 is associated with MAPK signaling pathway activation and indicate a possible novel mechanism in which Id-1 regulates prostate cancer cell growth and tumorigenesis.
螺旋-环-螺旋蛋白Id-1被认为在多种人类癌症的细胞增殖和肿瘤发生中发挥积极作用。然而，关于Id-1功能所涉及的分子机制却知之甚少。在本研究中，我们利用四个稳定的Id-1转染克隆，研究了MAPK信号通路在Id-1诱导的前列腺癌细胞非血清依赖性生长中的作用。我们的结果表明，在前列腺癌LNCaP细胞中瞬时和稳定的异位Id-1表达均导致Raf/MEK1/2信号通路的激活。此外，其抑制剂之一PD098059对MEK1/2磷酸化的抑制导致细胞周期S期比例和细胞生长速率降低，这表明MAPK信号通路的激活对于Id-1诱导的前列腺癌细胞增殖至关重要。此外，用与Id-1 mRNA互补的反义寡核苷酸处理PC-3和DU145细胞导致Id-1表达降低，同时Egr-1蛋白也减少。我们的结果首次表明Id-1的功能与MAPK信号通路激活有关，并提示了一种Id-1调节前列腺癌细胞生长和肿瘤发生的可能新机制。
