Garavello Werner, Nicolini Gabriella, Aguzzi Alessia, Maggioni Daniele, Leone Biagio Eugenio, Viganò Paola, Gaini Renato Maria, Tredici Giovanni
Department of Otorhinolaryngology - Head and Neck Surgery, 20052 Monza (MI), Italy.
Oncol Rep. 2006 Sep;16(3):479-84.
Mitogen-activated protein kinase (MAPK) cascades transmit and amplify signals involved in cell proliferation as well as in cell death. In this study, the potential derangement of MAPK pathways has been evaluated in human squamous cell carcinomas (SCC) of the larynx. The expression and activity of the MAPK p38, ERK1/2p44/p42 and JNK/SAPKp46/p54 have been investigated by immunoblot analysis of tissue homogenates in 27 samples of primary laryngeal cancer and in 27 paired non-neoplastic laryngeal mucosa. On the same tissues, the activation of MAPK JNK/SAPKp46/p54 was also analyzed by an ELISA assay. The results obtained showed that both total and phosphorylated levels of JNK/SAPKp46/p54 and p38 were not different between tumor and normal samples. Conversely, while total protein levels for both ERK1p44 and ERK2p42 were not statistically different between tumor and normal samples, the analysis of the level of the activated forms of ERK1/2 showed a statistically significant decreased phosphorylation of both isoforms in the tumor samples compared to the control tissues. The rate of reduction was similar for both isoforms. Immunohistochemical analysis of all the activated MAPK (p38, JNK/SAPKp46/p54 and ERK1/2p44/p42) in both laryngeal SCC and normal mucosa demonstrated no difference of cellular localization. Activated ERK1/2p44/p42 and activated p38 demonstrated a nucleo-cytoplasmic distribution whereas activated JNK/SAPKp46/p54 were localized into the cytoplasmic membrane. The decreased activity of ERK1/2p44/42 in laryngeal SCC might reflect alterations in tumor suppressing activity or might derive from the interplay among various transduction pathways.
丝裂原活化蛋白激酶（MAPK）级联反应可传递并放大参与细胞增殖和细胞死亡的信号。在本研究中，已对喉鳞状细胞癌（SCC）中MAPK信号通路的潜在紊乱情况进行了评估。通过对27份原发性喉癌样本及27份配对的非肿瘤性喉黏膜组织匀浆进行免疫印迹分析，研究了MAPK p38、ERK1/2 p44/p42和JNK/SAPK p46/p54的表达及活性。在相同组织上，还通过酶联免疫吸附测定（ELISA）分析了MAPK JNK/SAPK p46/p54的激活情况。所得结果显示，肿瘤样本与正常样本之间，JNK/SAPK p46/p54和p38的总水平及磷酸化水平均无差异。相反，虽然肿瘤样本与正常样本之间ERK1 p44和ERK2 p42的总蛋白水平无统计学差异，但对ERK1/2激活形式水平的分析显示，与对照组织相比，肿瘤样本中这两种亚型的磷酸化水平均有统计学意义的显著降低。两种亚型的降低率相似。对喉SCC和正常黏膜中所有激活的MAPK（p38、JNK/SAPK p46/p54和ERK1/2 p44/p42）进行免疫组织化学分析，结果表明细胞定位无差异。激活的ERK1/2 p44/p42和激活的p38呈核质分布，而激活的JNK/SAPK p46/p54定位于细胞膜。喉SCC中ERK1/2 p44/42活性降低可能反映了肿瘤抑制活性的改变，或者可能源于各种转导通路之间的相互作用。
