Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin
Differential ErbB1 signaling in squamous cell versus basal cell carcinoma of the skin
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DOI：
10.2353/ajpath.2007.060537
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Elder, James T.
中科院分区：
文献类型：
--
作者：
Rittie, Laure;Kansra, Sanjay;Elder, James T.
在这项研究中，我们检测了ErbB1信号在人体皮肤基底细胞癌和鳞状细胞癌（BCC和SCC）中的作用。我们使用酶联免疫吸附测定、激光捕获微解剖耦合实时逆转录聚合酶链反应和免疫组织化学来评估BCC和SCC肿瘤、基质和邻近表皮中ErbB1蛋白、配体和潜在下游效应物的表达和激活水平。尽管癌性皮肤和正常皮肤的ErbB1蛋白和mRNA总量相似，但我们发现，与BCC或正常皮肤相比，大块鳞状细胞癌的ErbB1激活（磷酸化- tyr(1068)）更大。此外，三种ErbB1配体转录物（双调节蛋白、肝素结合表皮生长因子样生长因子和转化生长因子-a）在SCC肿瘤细胞中上调，而在BCC中上调。与正常皮肤相比，这些配体的表达在临近鳞状细胞癌和基底细胞癌的无症状表皮中也有所增加。有趣的是，与其他配体相比，β细胞素转录水平被反向调节。同样，下游ErbB1效应物（Erk1/2和Akt）在SCC肿瘤细胞中被激活，而在BCC和BCC的邻近表皮中被激活。这些结果表明，ErbB1信号在鳞状细胞癌的肿瘤细胞中过度活跃，而在两种肿瘤类型的肿瘤细胞和附近的无症状表皮中则没有。我们的研究结果表明，靶向ErbB1信号可能有益于治疗SCC。
in this study, we examined ErbB1 signaling in human basal and squamous cell carcinomas (BCC and SCC) of the skin in vivo. We used enzyme-linked immunosorbent assay, laser capture microdissection-coupled real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry to assess expression and activation levels of ErbB1 protein, ligands, and potential downstream effectors, in BCC and SCC tumors, stroma, and adjacent epidermis. Although total ErbB1 protein and mRNA were similar in cancerous and normal skin, we found that ErbB1 activation (phospho-Tyr(1068)) was greater in bulk SCC versus BCC or normal skin. in addition, three ErbB1 ligand transcripts (amphiregulin, heparin-binding epidermal growth factor-like growth factor, and transforming growth factor-a) were up-regulated in tumor cells of SCC but not BCC. Expression of these ligands was also increased in asymptomatic epidermis adjacent to both SCC and BCC, relative to normal skin. Interestingly, betacellulin transcript levels were inversely regulated compared with the other ligands. Consistently, downstream ErbB1 effectors (Erk1/2 and Akt) were activated in tumor cells of SCC but not of BCC and in adjacent epidermis of both BCC and SCC. These results demonstrate that ErbB1 signaling is hyperactive in tumor cells of SCC but not of BCC and in nearby asymptomatic epidermis of both tumor types. Our results suggest that targeting ErbB1 signaling might be of benefit in the treatment of SCC.