Role of c-myc protein in hormone refractory prostate carcinoma: cellular response to paclitaxel
Role of c-myc protein in hormone refractory prostate carcinoma: cellular response to paclitaxel
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DOI：
10.1016/j.bcp.2004.06.002
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发表时间：
2004-09-01
影响因子：
5.8
通讯作者：
Zunino, F
中科院分区：
文献类型：
--
作者：
Cassinelli, G;Supino, R;Zunino, F
原癌基因c-myc扩增是激素难治性前列腺癌(HRPC)的常见改变。为了研究c-myc在细胞对紫杉醇(PTX)的反应中的作用，我们使用了两个HRPC细胞系DU145和PC3，它们具有不同的蛋白质水平和对紫杉烷的不同反应行为。在两种细胞系中，PTX诱导的细胞死亡均为caspase介导的细胞死亡。在DU145细胞中，PTX诱导了与c-myc上调相关的早期凋亡反应，仅限于G2/M细胞群体。在c-myc反义(AS-c-myc)存在的情况下，这一事件似乎延迟了，表明该蛋白的表达受到上游调控。此外，反义方法提供了c-myc参与紫杉烷诱导的细胞凋亡反应的证据。在PC3细胞中，过表达的c-myc不受药物处理的调节，AS-c-myc的加入不影响PTX对细胞生长的抑制。在两种细胞系中，PTX诱导的c-myc磷酸化伴随有丝分裂停滞，与AKT和MAPK激酶激活状态的调节无关。我们的数据表明，HRPC细胞对PTX的细胞反应可能涉及c-myc，并提示其促凋亡作用受遗传背景的影响，从而支持HRPC细胞对紫杉烷的复杂和差异性反应。(C)2004 Elsevier Inc.保留所有权利。
Amplification of the c-MYC proto-oncogene is a frequent alteration in hormone refractory prostate carcinomas (HRPC). In an attempt to investigate the role of c-myc in the cellular response to paclitaxel (PTX), we used two HRPC cell lines, DU145 and PC3, characterised by different levels of the protein and by different behaviour in response to taxane. In both cell lines, PTX-induced cell death was a caspase-mediated apoptosis. In DU145 cells, PTX induced an early apoptotic response associated with upregulation of c-myc restricted to the G2/ M cell population. This event appeared delayed in the presence of c-myc antisense (AS-c-myc), suggesting an upstream regulation of the protein expression. In addition, the antisense approach provided evidence of an involvement of c-myc in the apoptotic response to the taxane. In contrast, in PC3 cells, the overexpressed c-myc was not modulated by drug-treatment and the addition of AS-c-myc did not affect the cell growth inhibition of PTX. In both cell lines, PTX-induced c-myc phosphorylation was concomitant with the mitotic arrest and not related to the modulation of the activation state of AKT and MAPK kinases. Our data indicate that the cellular response to PTX of HRPC cells can involve c-myc and suggest that its pro-apoptotic role is affected by the genetic background, thus supporting a complex and differentiated HRPC cell response to taxanes. (C) 2004 Elsevier Inc. All rights reserved.