Murakami A, Suminami Y, Hirakawa H, Nawata S, Numa F, Kato H
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube 755-8505, Japan.
Br J Cancer. 2001 Mar 23;84(6):851-8. doi: 10.1054/bjoc.2000.1683.
Previous study has demonstrated that squamous cell carcinoma antigen (SCCA) 1 attenuates apoptosis induced by TNF alpha, NK cell or anticancer drug. In this study, we have examined the effect of SCCA2, which is highly homologous to SCCA1, but has different target specificity, against radiation-induced apoptosis, together with that of SCCA1. We demonstrated that cell death induced by radiation treatment was remarkably suppressed not only in SCCA1 cDNA-transfected cells, but also in SCCA2 cDNA-transfected cells. In these transfectants, caspase 3 activity and the expression of activated caspase 9 after radiation treatment were suppressed. Furthermore, the expression level of phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) was suppressed compared to that of the control cells. The expression level of upstream stimulator of p38 MAPK, phosphorylated MKK3/MKK6, was also suppressed in the radiation-treated cells. Thus, both SCCA1 and SCCA2 may contribute to survival of the squamous cells from radiation-induced apoptosis by regulating p38 MAPK pathway.
先前的研究表明，鳞状细胞癌抗原（SCCA）1可减轻由肿瘤坏死因子α、自然杀伤细胞或抗癌药物诱导的细胞凋亡。在本研究中，我们检测了与SCCA1高度同源但具有不同靶标特异性的SCCA2对辐射诱导的细胞凋亡的影响，以及SCCA1的影响。我们证明，辐射处理诱导的细胞死亡不仅在转染了SCCA1 cDNA的细胞中显著受到抑制，在转染了SCCA2 cDNA的细胞中也受到显著抑制。在这些转染细胞中，辐射处理后caspase 3活性和活化的caspase 9的表达受到抑制。此外，与对照细胞相比，磷酸化的p38丝裂原活化蛋白激酶（p38 MAPK）的表达水平受到抑制。在辐射处理的细胞中，p38 MAPK的上游刺激物磷酸化的MKK3/MKK6的表达水平也受到抑制。因此，SCCA1和SCCA2可能都通过调节p38 MAPK途径，有助于鳞状细胞在辐射诱导的细胞凋亡中存活。
