Squamous cell carcinoma antigen suppresses radiation-induced cell death.

Squamous cell carcinoma antigen suppresses radiation-induced cell death.
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DOI:
10.1054/bjoc.2000.1683
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发表时间:
2001-03-23
影响因子:
8.8
通讯作者:
Kato, H
Kato, H
中科院分区:
医学1区
文献类型:
--
作者:
Murakami, A;Suminami, Y;Hirakawa, H;Nawata, S;Numa, F;Kato, H

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先前的研究表明,鳞状细胞癌抗原(SCCA)1可减弱TNFα、NK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点特异性的 SCCA2 与 SCCA1 一起对抗辐射诱导的细胞凋亡的作用。我们证明,放射治疗诱导的细胞死亡不仅在 SCCA1 cDNA 转染的细胞中得到显着抑制,而且在 SCCA2 cDNA 转染的细胞中也得到显着抑制。在这些转染子中,放射治疗后 caspase 3 活性和活化 caspase 9 的表达受到抑制。此外,与对照细胞相比,磷酸化p38丝裂原激活蛋白激酶(p38 MAPK)的表达水平受到抑制。 p38 MAPK 上游刺激物(磷酸化 MKK3/MKK6)的表达水平在放射处理的细胞中也受到抑制。因此,SCCA1和SCCA2可能通过调节p38 MAPK通路来促进鳞状细胞在辐射诱导的细胞凋亡中的存活。 © 2001 癌症研究运动 http://www.bjcancer.com
Previous study has demonstrated that squamous cell carcinoma antigen (SCCA) 1 attenuates apoptosis induced by TNFα, 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. © 2001 Cancer Research Campaign http://www.bjcancer.com