Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma
Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma
复制标题
DOI：
10.1016/s0002-9440(10)64408-2
复制
发表时间：
2002-10-01
影响因子：
6
通讯作者：
Hampton, GM
中科院分区：
文献类型：
--
作者：
Frierson, HF;Ei-Naggar, AK;Hampton, GM
涎腺癌包括一组异质性肿瘤，其生物学和临床特征与头颈部粘膜鳞状细胞癌有很大不同。腺样囊性癌（ACC）是最常见的亚型之一，以其肌上皮分化、血行播散倾向和缓慢但进行性的临床过程而闻名。其发展和进展的分子变化的特点是很差的。在这里，我们使用寡核苷酸芯片分析，调查8920个不同的人类基因在15个ACC，ACC细胞系，和5个正常的大涎腺的表达。正如预期的那样，我们观察到了指示肌上皮分化的基因的表达，包括那些蛋白质产物是基底膜和细胞外基质成分的基因。其他在ACC中高度表达的基因是那些编码转录因子SOX 4和AP-2 γ的基因，相对于我们先前分析的10个解剖部位的175个其他癌症，后者在ACC中也过表达。与其他癌相比，ACC中高表达的其他基因包括酪蛋白激酶1、cytokine和frizzled-7，两者都是Wnt/β-连环蛋白信号通路的成员。我们的研究首次记录了ACC中过表达的基因的多样性，并强调了未来可能被用作这种癌症的治疗靶点的基因产物和途径，到目前为止，这种癌症对化疗方法的反应有限。
Salivary gland cancers comprise a heterogeneous group of neoplasms whose biological and clinical characteristics differ considerably from those of mucosal squamous cell carcinomas of the head and neck. One of the most common subtypes, adenoid cystic carcinoma (ACC), is notable for its myoepithelial differentiation, proclivity for hematogenous spread, and slow but progressive clinical course. The molecular alterations that underlie its development and progression are poorly characterized. Here we used oligonucleotide microarray analysis to survey the expression of 8920 different human genes in 15 ACCs, one ACC cell line, and five normal major salivary glands. We observed expression of genes indicative of myoepithelial differentiation, as expected, including those whose protein products are components of basement membranes and extracellular matrix. Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2gamma, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled. Additional genes, which were highly expressed in ACC compared to the other carcinomas, included casein kinase 1, epsilon and frizzled-7, both members of the Wnt/beta-catenin signaling pathway. Our study documents for the first time the diverse spectrum of genes overexpressed in ACC and highlights gene products and pathways that in the future might be exploited as therapeutic targets for this cancer, which up until now, has shown limited response to chemotherapeutic approaches.