Huang C, Ma W Y, Ryan C A, Dong Z
The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):11957-62. doi: 10.1073/pnas.94.22.11957.
Solar UV irradiation is the causal factor for the increasing incidence of human skin carcinomas. The activation of the transcription factor activator protein-1 (AP-1) has been shown to be responsible for the tumor promoter action of UV light in mammalian cells. We demonstrate that proteinase inhibitor I (Inh I) and II (Inh II) from potato tubers, when applied to mouse epidermal JB6 cells, block UV-induced AP-1 activation. The inhibition appears to be specific for UV-induced signal transduction for AP-1 activation, because these inhibitors did not block UV-induced p53 activation nor did they exhibit any significant influence on epidermal growth factor-induced AP-1 transactivation. Furthermore, the inhibition of UV-induced AP-1 activity occurs through a pathway that is independent of extracellular signal-regulated kinases and c-Jun N-terminal kinases as well as P38 kinases. Considering the important role of AP-1 in tumor promotion, it is possible that blocking UV-induced AP-1 activity by Inh I or Inh II may be functionally linked to irradiation-induced cell transformation.
日光紫外线照射是人类皮肤癌发病率上升的致病因素。转录因子激活蛋白-1（AP-1）的激活已被证明是紫外线在哺乳动物细胞中促肿瘤作用的原因。我们证明，来自马铃薯块茎的蛋白酶抑制剂I（Inh I）和II（Inh II）应用于小鼠表皮JB6细胞时，可阻断紫外线诱导的AP-1激活。这种抑制似乎对紫外线诱导的AP-1激活信号转导具有特异性，因为这些抑制剂既不阻断紫外线诱导的p53激活，也对表皮生长因子诱导的AP-1反式激活没有任何显著影响。此外，紫外线诱导的AP-1活性抑制是通过一条独立于细胞外信号调节激酶、c-Jun N端激酶以及P38激酶的途径发生的。考虑到AP-1在肿瘤促进中的重要作用，Inh I或Inh II阻断紫外线诱导的AP-1活性可能在功能上与辐射诱导的细胞转化有关。
