Fang Min, Wee Sue Ann, Ronski Karyn, Fan Hongran, Tao Shiying, Lin Qun
Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Butler Bldg. 5, Farmington, CT, 06030-6140, USA,
Genomic Med. 2007;1(1-2):75-85. doi: 10.1007/s11568-007-9010-9. Epub 2007 Jul 25.
Hyperproliferative epidermal disorders range from benign hyperplasias such as psoriasis to basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the two most common cancers in the US. While they all arise from the epidermis, these diseases differ dramatically in biological behavior and their underlying gene expression patterns have not been compared. We thus examined mRNA transcript levels in these disorders to identify and further characterize differentially expressed genes. Transcript expression patterns distinguish these disorders and identify EGR1, among other genes, whose epidermal expression is decreased in BCC and SCC but is elevated in psoriasis. Egr-1 inhibits growth of benign and malignant epidermal cells in vitro and appears to suppress both Cdc25A expression and Cdk2 dephosphorylation. These data indicate that gene expression profiling can differentiate epidermal hyperproliferative diseases and suggest that Egr-1 may play a role in preventing uncontrolled epidermal growth.
增殖性表皮疾病范围广泛,从良性增生如银屑病到基底细胞癌(BCC)和鳞状细胞癌(SCC),这两种是美国最常见的癌症。虽然它们都起源于表皮,但这些疾病在生物学行为上有显著差异,且其潜在的基因表达模式尚未进行比较。因此,我们检测了这些疾病中的mRNA转录水平,以鉴定并进一步表征差异表达基因。转录表达模式区分了这些疾病,并鉴定出了早期生长反应蛋白1(EGR1)等基因,其在表皮中的表达在基底细胞癌和鳞状细胞癌中降低,但在银屑病中升高。Egr-1在体外抑制良性和恶性表皮细胞的生长,并且似乎抑制细胞周期蛋白依赖性激酶25A(Cdc25A)的表达和细胞周期蛋白依赖性激酶2(Cdk2)的去磷酸化。这些数据表明,基因表达谱分析可以区分表皮增殖性疾病,并提示Egr-1可能在预防表皮失控生长中发挥作用。