p63 expression defines a lethal subset of muscle-invasive bladder cancers.
p63 expression defines a lethal subset of muscle-invasive bladder cancers.
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DOI：
10.1371/journal.pone.0030206
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Siefker-Radtke A
中科院分区：
文献类型：
--
作者：
Choi W;Shah JB;Tran M;Svatek R;Marquis L;Lee IL;Yu D;Adam L;Wen S;Shen Y;Dinney C;McConkey DJ;Siefker-Radtke A
P63是P53家族中的一员，与上皮干细胞隔间的维持有关。以前的研究表明，p63在肌肉浸润性膀胱癌中表达下调，但p63表达与生存的关系尚不清楚。我们用实时荧光定量聚合酶链式反应研究了人膀胱癌细胞系(n = 15)和原发肿瘤细胞系(n = 10 1)中p63的表达以及与上皮向间充质转化有关的几个基因。我们将肿瘤标记物的表达与分期、疾病特异性(DSS)和总生存期(OS)相关联。E-钙粘蛋白和p63的表达呈正相关，与间充质标志物ZEB-1、ZEB-2和Vimentin的表达呈负相关。非肌肉浸润性膀胱癌(Ta和T1)均高水平表达E-钙粘蛋白和p63，低水平表达间充质标志物。有趣的是，肌肉侵袭性(T2-T4)肿瘤的一部分维持高水平的E-钙粘素和p63表达。正如预期的那样，肌间质瘤标记物的表达与肌肉侵袭有很强的相关性(p<；0.0001)。然而，在保留P63的肌肉浸润性肿瘤患者中，OS较短(p = 0.007)。我们的数据证实EMT的分子标记在肌肉浸润性膀胱癌中升高，但有趣的是，在肌肉浸润性肿瘤中保留“上皮”标记p63与更差的预后相关。
p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear. We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n = 15) and primary tumors (n = 101). We correlated tumor marker expression with stage, disease-specific (DSS), and overall survival (OS). Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1) bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2–T4) tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p<0.0001). However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007). Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the “epithelial” marker p63 in muscle-invasive tumors is associated with a worse outcome.
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影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0906549106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Chan, Keith Syson;Espinosa, Inigo;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
11.2
作者：
Hurteau, Gregory J.;Carlson, J. Andrew;Brock, Graham J.
通讯作者：
Brock, Graham J.
影响因子：
37.3
作者：
Kim WJ;Kim EJ;Kim SK;Kim YJ;Ha YS;Jeong P;Kim MJ;Yun SJ;Lee KM;Moon SK;Lee SC;Cha EJ;Bae SC
通讯作者：
Bae SC
DOI：
10.1152/ajprenal.00533.2007
发表时间：
2008-06-01
影响因子：
4.2
作者：
Kurzrock, Eric A.;Lieu, Deborah K.;Isseroff, Roslyn R.
通讯作者：
Isseroff, Roslyn R.