Serewko Magdalena M, Popa Claudia, Dahler Alison L, Smith Louise, Strutton Geoff M, Coman William, Dicker Anthony J, Saunders Nicholas A
Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland, Woolloongabba, Australia.
Cancer Res. 2002 Jul 1;62(13):3759-65.
This study focuses on characterizing the genetic and biological alterations associated with squamous cell carcinoma development. Normal human epidermal keratinocytes (HEKs), cells isolated from a preneoplastic lesion (IEC-1), and two neoplastic cell lines, SCC-25 and COLO-16, were grown as raft cultures, and their gene expression profiles were screened using cDNA arrays. Our data indicated that the expression levels of at least 37 genes were significantly (P <or= 0.05; 1.9% of genes screened) altered in neoplastic cells compared with normal cells. Of these genes, 10 genes were up-regulated and 27 genes were down-regulated in the neoplastic cells. In addition, 51% of the genes altered in the neoplastic cells were already altered in the preneoplastic IEC-1 cells. Immunohistochemical staining of patient tumors was used to verify the cDNA array analysis. Our analysis indicated that alterations in genes associated with extracellular matrix production and apoptosis are disrupted in preneoplastic cells, whereas later stages of neoplasia are associated with alterations in gene expression for genes involved in DNA repair or epidermal growth factor (EGF) receptor/mitogen-activated protein kinase kinase (MAPKK)/MAPK/activator protein-1 (AP-1) signaling. Subsequent functional analysis of the alterations in expression of the EGF receptor/MAPKK/MAPK/AP-1 genes suggested they did not contribute to the neoplastic phenotype.
本研究聚焦于表征与鳞状细胞癌发生相关的基因和生物学改变。将正常人表皮角质形成细胞（HEK）、从癌前病变中分离出的细胞（IEC-1）以及两种肿瘤细胞系SCC-25和COLO-16培养成筏状培养物，并使用cDNA阵列筛选它们的基因表达谱。我们的数据表明，与正常细胞相比，肿瘤细胞中至少37个基因的表达水平发生了显著改变（P≤0.05；占筛选基因的1.9%）。在这些基因中，肿瘤细胞中有10个基因上调，27个基因下调。此外，肿瘤细胞中改变的基因有51%在癌前IEC-1细胞中已经发生了改变。对患者肿瘤进行免疫组织化学染色以验证cDNA阵列分析。我们的分析表明，与细胞外基质产生和凋亡相关的基因改变在癌前细胞中就已被破坏，而肿瘤形成的后期阶段与参与DNA修复或表皮生长因子（EGF）受体/丝裂原活化蛋白激酶激酶（MAPKK）/丝裂原活化蛋白激酶（MAPK）/活化蛋白-1（AP-1）信号传导的基因表达改变有关。随后对EGF受体/MAPKK/MAPK/AP-1基因表达改变的功能分析表明，它们对肿瘤表型没有贡献。
