Targets of Wnt/ß-catenin transcription in penile carcinoma.
Targets of Wnt/ß-catenin transcription in penile carcinoma.
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DOI：
10.1371/journal.pone.0124395
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Ahmed A
中科院分区：
文献类型：
--
作者：
Arya M;Thrasivoulou C;Henrique R;Millar M;Hamblin R;Davda R;Aare K;Masters JR;Thomson C;Muneer A;Patel HR;Ahmed A
阴茎鳞状细胞癌（PeCa）是一种罕见的恶性肿瘤，人们对 PeCa 致癌的分子机制知之甚少。 Wnt 信号通路以转录激活剂 ß-连环蛋白作为主要转导因子，是发育和疾病（尤其是癌症）过程中的关键细胞通路。我们使用 PeCa 组织阵列和多荧光团标记的定量免疫组织化学来检测 WNT4（一种 Wnt 配体）和 Wnt-ß-catenin 转录激活的三个靶标（即 MMP7、cyclinD1 (CD1) 和 c-MYC）在来自 101 个独特样本的 141 个阴茎组织核心中的表达。与对照组织（正常或癌旁）样本相比，PeCa 样本中所有测试的 Wnt 信号蛋白的表达增加了 1.6 至 3 倍（p<0.01）。与 I 级肿瘤相比，II 级肿瘤中除 CD1 外的所有蛋白质的表达均显着下降。使用高放大倍率、去卷积共焦图像来测量四种蛋白质之间共定位的差异。对于蛋白质组合和组织状态（对照、I级和II级肿瘤）的各种排列，观察到显着（p<0.04-0.0001）差异。 Wnt 信号传导可能在 PeCa 中发挥重要作用，并且 Wnt 信号传导网络的蛋白质可能是疾病诊断和预后分层的有用靶标。
Penile squamous cell carcinoma (PeCa) is a rare malignancy and little is known regarding the molecular mechanisms involved in carcinogenesis of PeCa. The Wnt signaling pathway, with the transcription activator ß-catenin as a major transducer, is a key cellular pathway during development and in disease, particularly cancer. We have used PeCa tissue arrays and multi-fluorophore labelled, quantitative, immunohistochemistry to interrogate the expression of WNT4, a Wnt ligand, and three targets of Wnt-ß-catenin transcription activation, namely, MMP7, cyclinD1 (CD1) and c-MYC in 141 penile tissue cores from 101 unique samples. The expression of all Wnt signaling proteins tested was increased by 1.6 to 3 fold in PeCa samples compared to control tissue (normal or cancer adjacent) samples (p<0.01). Expression of all proteins, except CD1, showed a significant decrease in grade II compared to grade I tumors. High magnification, deconvolved confocal images were used to measure differences in co-localization between the four proteins. Significant (p<0.04-0.0001) differences were observed for various permutations of the combinations of proteins and state of the tissue (control, tumor grades I and II). Wnt signaling may play an important role in PeCa and proteins of the Wnt signaling network could be useful targets for diagnosis and prognostic stratification of disease.
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