Sanchez-Carbayo Marta, Schwarz Karin, Charytonowicz Elizabeth, Cordon-Cardo Carlos, Mundel Peter
Division of Molecular Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, NY 10021, USA.
Oncogene. 2003 Aug 14;22(34):5298-305. doi: 10.1038/sj.onc.1206616.
Myopodin is a dual compartment protein that displays actin-bundling activity and redistributes between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. We evaluated myopodin expression in initiation and progression of bladder cancer. Normal urothelium expresses myopodin in the cytoplasm and nuclei. Invasive bladder tumors showed decreased nuclear myopodin expression as compared to superficial lesions. This loss of nuclear myopodin expression was significantly associated with histopathological stage, tumor grade and overall patient survival in bladder tumors contained in tissue microarrays. We identified a differential nuclear expression for myopodin among bladder cancer cell lines during cell-cycle. Myopodin was present in the nucleus during G1/S in cells derived from superficial and low-grade lesions but not in those derived from invasive tumors. Loss of nuclear myopodin expression could classify bladder tumors and bladder cancer cell lines based on their histopathology. Most importantly, patients with preserved nuclear myopodin expression showed a longer survival. Nuclear myopodin expression in the context of cell-cycle progression may prove useful for staging bladder tumors and suggest a tumor suppressor role of myopodin in bladder cancer.
肌动蛋白结合蛋白是一种双区室蛋白，具有肌动蛋白成束活性，并以分化依赖性和应激诱导的方式在细胞核和细胞质之间重新分布。我们评估了肌动蛋白结合蛋白在膀胱癌发生和发展过程中的表达情况。正常尿路上皮细胞的细胞质和细胞核中均表达肌动蛋白结合蛋白。与浅表性病变相比，浸润性膀胱肿瘤的细胞核肌动蛋白结合蛋白表达降低。在组织微阵列中的膀胱肿瘤中，细胞核肌动蛋白结合蛋白表达的丧失与组织病理学分期、肿瘤分级及患者总体生存率显著相关。我们发现在细胞周期中，膀胱癌细胞系之间肌动蛋白结合蛋白的细胞核表达存在差异。在G1/S期，来源于浅表性和低级别病变的细胞中肌动蛋白结合蛋白存在于细胞核中，而来源于浸润性肿瘤的细胞则不然。细胞核肌动蛋白结合蛋白表达的丧失可根据组织病理学对膀胱肿瘤和膀胱癌细胞系进行分类。最重要的是，细胞核肌动蛋白结合蛋白表达保留的患者生存期更长。细胞周期进程中细胞核肌动蛋白结合蛋白的表达可能对膀胱肿瘤分期有用，并提示肌动蛋白结合蛋白在膀胱癌中具有肿瘤抑制作用。
