de Lima Marina de Deus Moura, Marques Yonara Maria Freire Soares, Alves Sérgio de Melo, Freitas Vanessa Morais, Soares Fernando Augusto, de Araújo Vera Cavalcanti, Pinto Décio dos Santos, Mantesso Andrea
Oral Pathology Department, School of Dentistry, University of São Paulo, São Paulo, SP, Brazil.
Cancer Epidemiol. 2009 Aug;33(2):142-6. doi: 10.1016/j.canep.2009.04.016. Epub 2009 Jun 6.
MDM2, P53, P21(WAF1) and pAKT are proteins associated with the balance between cell death and survival. There are many hypotheses regarding the role of these proteins in salivary gland tumours. However, many molecular events that activate or inactivate regulatory genes remain unknown. The aim of this study was to evaluate and to correlate MDM2, P53, P21(WAF1) and pAKT protein expressions in adenoid cystic carcinomas (ACC).
Twenty-two cases of ACC were evaluated by immunohistochemistry and one cell line derived from ACC was analyzed by Western Blotting and immunofluorescence techniques.
Strong MDM2 and pAKT, variable P53 and null P21 expressions were found in the cases analyzed, but no statistical correlation was established when comparing MDM2 and pAKT expressions in the 3 different ACC subtypes. The ACC cell line showed intense nuclear and cytoplasmatic MDM2 and pAKT expressions and null P53 and P21 expressions.
Results indicate that MDM2 and pAKT are related to the tumorigenesis of ACC, but they might not be directly connected to tumour progression. We also demonstrate that the pAKT pathway is active in ACC and it seems to be activating the MDM2 shuttle from the cytoplasm to the nucleus, where it phosphorylates P53 and carries it to the cytoplasm for degradation.
MDM2、P53、P21（WAF1）和磷酸化AKT（pAKT）是与细胞死亡和存活平衡相关的蛋白质。关于这些蛋白质在涎腺肿瘤中的作用有许多假说。然而，许多激活或失活调控基因的分子事件仍不清楚。本研究的目的是评估腺样囊性癌（ACC）中MDM2、P53、P21（WAF1）和pAKT蛋白的表达并进行相关性分析。
采用免疫组织化学方法对22例ACC病例进行评估，并采用蛋白质印迹法和免疫荧光技术对1株ACC细胞系进行分析。
在所分析的病例中发现MDM2和pAKT表达强，P53表达可变，P21表达缺失，但在比较3种不同ACC亚型中MDM2和pAKT的表达时未建立统计学相关性。ACC细胞系显示MDM2和pAKT在细胞核和细胞质中强烈表达，P53和P21表达缺失。
结果表明MDM2和pAKT与ACC的肿瘤发生有关，但它们可能与肿瘤进展无直接关联。我们还证明pAKT通路在ACC中是活跃的，并且似乎在激活MDM2从细胞质穿梭到细胞核，在细胞核中它使P53磷酸化并将其转运到细胞质中进行降解。
