Jing Ling, Liu Lijun, Yu Yan Ping, Dhir Rajiv, Acquafondada Marie, Landsittel Doug, Cieply Kathleen, Wells Alan, Luo Jian-Hua
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Am J Pathol. 2004 May;164(5):1799-806. doi: 10.1016/S0002-9440(10)63738-8.
Myopodin was previously reported as a gene that was frequently deleted in prostate cancer. This gene shares significant homology with a cell shape-regulating gene, synaptopodin. Myopodin was shown to bind actin and to induce actin bundling when cells were stimulated. To clarify the functional role of myopodin in prostate cancer, several assays were performed to evaluate the tumor suppression activity of myopodin. Our results indicate that myopodin inhibits tumor growth and invasion both in vitro and in vivo. The activity of tumor suppression of myopodin is located at the C-terminus region. To further evaluate the role of myopodin in suppressing the invasiveness of prostate cancer, an expression analysis of myopodin protein was performed in prostate tissues. The results indicate that down-regulation of myopodin expression occurs mostly in invasive stages of prostate cancer, implying a potential invasion suppression role for myopodin in prostate cancer. In addition, hemizygous deletion and down-regulation of myopodin expression occur in three aggressive prostate cancer cell lines. All these results support the hypothesis that myopodin functions as a tumor suppressor gene to limit the growth and to inhibit the metastasis of cancer cells.
肌动蛋白结合蛋白(Myopodin)先前被报道为一种在前列腺癌中经常缺失的基因。该基因与一种细胞形态调节基因——突触素(synaptopodin)具有显著的同源性。当细胞受到刺激时,肌动蛋白结合蛋白被证明能结合肌动蛋白并诱导肌动蛋白成束。为了阐明肌动蛋白结合蛋白在前列腺癌中的功能作用,我们进行了多项实验来评估肌动蛋白结合蛋白的肿瘤抑制活性。我们的结果表明,肌动蛋白结合蛋白在体外和体内均能抑制肿瘤生长和侵袭。肌动蛋白结合蛋白的肿瘤抑制活性位于其C末端区域。为了进一步评估肌动蛋白结合蛋白在抑制前列腺癌侵袭性中的作用,我们对前列腺组织中的肌动蛋白结合蛋白进行了表达分析。结果表明,肌动蛋白结合蛋白表达下调主要发生在前列腺癌的侵袭阶段,这意味着肌动蛋白结合蛋白在前列腺癌中可能具有抑制侵袭的作用。此外,在三种侵袭性前列腺癌细胞系中发生了肌动蛋白结合蛋白的半合子缺失和表达下调。所有这些结果支持了这样一种假说,即肌动蛋白结合蛋白作为一种肿瘤抑制基因,可限制癌细胞的生长并抑制其转移。