Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells
Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells
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DOI：
10.1002/jcp.21130
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发表时间：
2007-11-01
影响因子：
5.6
通讯作者：
Cittadini, A.
中科院分区：
文献类型：
--
作者：
Sgambato, A.;De Paola, B.;Cittadini, A.
前列腺癌是西方男性中最常诊断的癌症，在临床侵袭性和预后方面可以显示出高度的可变性，并且没有可用的标志物能够准确地预测其临床过程。Dystroglycan（DG）是一种非整联蛋白粘附分子，由α-DG和β-DG两个亚基形成复合物，分别与细胞外基质分子和细胞骨架结合。DG表达在人类癌症中经常减少，并且与肿瘤分级和侵袭性有关。本研究探讨了DG在人前列腺肿瘤发生中的作用及其作为预后标志物的适用性。细胞外α-DG亚基的表达水平在人前列腺癌细胞系和原发性肿瘤中经常降低，并且与治疗前样本（中位数= 28%）相比，雄激素消融治疗后体内阳性肿瘤细胞的百分比（中位数= 1%）显著进一步降低。在治疗后样品上的α-DG染色与肿瘤复发之间观察到显著关系。一个密切的和时间依赖性的DG表达减少也发生在人前列腺癌细胞治疗后，与抗雄激素flutamine。外源性DG cDNA在LNCaP人前列腺癌细胞系中的稳定表达导致对锚定依赖性和独立性生长以及体内致瘤性的显著抑制。这些发现证实并扩展了先前的证据，即DG复合物功能的紊乱可能有助于前列腺癌细胞恶性行为的定义，并表明雄激素可能调节这些细胞中DG的表达。
Prostate cancer, the most frequently diagnosed cancer in Western men, can display a high variability in term of clinical aggressiveness and prognosis and none of the available markers is able to accurately predict its clinical course. Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton, respectively. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. This study investigated the role of DG in human prostate tumorigenesis and its suitability as a prognostic marker. The expression level of extracellular alpha-DG subunit was frequently reduced in human prostate cancer cell lines and primary tumors and the percentage of positive tumor cells was significantly further decreased in vivo following androgen ablation therapy (median = 1%) compared to pre-treatment samples (median = 28%). A significant relationship was observed between alpha-DG staining on the post-treatment samples and tumor recurrence. A close- and time-dependent decrease of DG expression also occurred in human prostate cancer cells following treatment with the anti-androgen flutamide. Stable expression of an exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a marked inhibition of both anchorage-dependent and independent growth and of the in vivo tumorigenicity. These findings confirm and extend previous evidence that disturbances in the function of the DG complex might contribute to the definition of the malignant behavior of prostate cancer cells and suggest that androgens might regulate DG expression in these cells.