Hamada K, Shinomiya H, Asano Y, Kihana T, Iwamoto M, Hanakawa Y, Hashimoto K, Hirose S, Kyo S, Ito M
Department of Obstetrics and Gynecology, School of Medicine, Ehime University, Shitsukawa, Shigenobu, Osen-gun, Ehime 791-0295, Japan.
Biochim Biophys Acta. 2001 Mar 19;1518(1-2):124-31. doi: 10.1016/s0167-4781(01)00174-9.
The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2, which are 95% identical in nucleotide sequence. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. We analyzed here the sequence and the promoter activity of the 5'-flanking region of the SCCA1 gene. Deletion analysis of SCCA1 and SCCA2 promoter identified a 471-bp core promoter region upstream of the transcription start site. The transcriptional activity of SCCA1 promoter was up-regulated in squamous cell carcinoma cells, compared with keratinocyte and adenocarcinoma cells. The ratios of SCCA1 to SCCA2 promoter activity in squamous cell carcinoma, keratinocyte and adenocarcinoma cells were respectively 1.6, 5.3 and 2.8. Position -50 of SCCA1 and SCCA2 promoters played an important role in determining the promoter activities of SCCA1 and SCCA2. These findings suggest that the transcriptional regulation of SCCA1 and SCCA2 might differ among squamous cell carcinoma, keratinocyte and adenocarcinoma cells, and that SCCA1 promoter might be a potential target of gene therapy for squamous cell carcinoma.
鳞状细胞癌抗原（SCCA）是鳞状细胞癌的一种血清学标志物。SCCA基因组区域的分子克隆揭示了两个串联排列的基因SCCA1和SCCA2的存在，它们在核苷酸序列上有95%的同一性。SCCA1是一种木瓜蛋白酶样半胱氨酸蛋白酶抑制剂，而SCCA2是一种胰凝乳蛋白酶样丝氨酸蛋白酶抑制剂。我们在此分析了SCCA1基因5'侧翼区域的序列和启动子活性。对SCCA1和SCCA2启动子的缺失分析确定了转录起始位点上游一个471bp的核心启动子区域。与角质形成细胞和腺癌细胞相比，SCCA1启动子的转录活性在鳞状细胞癌细胞中上调。鳞状细胞癌、角质形成细胞和腺癌细胞中SCCA1与SCCA2启动子活性的比值分别为1.6、5.3和2.8。SCCA1和SCCA2启动子的-50位在决定SCCA1和SCCA2的启动子活性中起重要作用。这些发现表明，SCCA1和SCCA2的转录调控在鳞状细胞癌、角质形成细胞和腺癌细胞中可能不同，并且SCCA1启动子可能是鳞状细胞癌基因治疗的一个潜在靶点。
