Rosen C F, Gajic D, Drucker D J
Department of Medicine, Women's College Hospital, Toronto, Ontario, Canada.
Cancer Res. 1990 May 1;50(9):2631-5.
UV radiation plays an important role in the induction of cutaneous malignancy, including basal cell and squamous cell carcinomas and malignant melanoma. In addition to its effects on DNA damage and repair mechanisms, UV radiation has been shown to modulate the expression of specific genes, altering the levels of their mRNAs and the synthesis of their corresponding proteins. In order to gain further information about the molecular effects of UV radiation, we have studied the regulation of ornithine decarboxylase (ODC) gene expression in response to UVB radiation. ODC is the rate-limiting enzyme in polyamine biosynthesis, is involved in growth and differentiation, and has been implicated in carcinogenesis. Keratinocytes grown in culture were either sham-irradiated or exposed to increasing doses of UVB (1-5 mJ/cm2). Northern blot analysis of keratinocyte RNA under basal conditions demonstrated the presence of two ODC mRNA transcripts. Increasing exposure to UVB resulted in a dose-dependent increase in the levels of both ODC mRNA transcripts. The induction of ODC gene expression following UVB was noted 2 h after UVB exposure, and ODC mRNA levels continued to increase up to 24 h after UVB exposure. The UVB-induced increase in ODC gene expression was not serum dependent, despite the ability of serum alone to induce ODC gene expression. The mRNA transcripts for actin and hexosaminidase A were not induced after UVB exposure. These studies show that the UVB-induced increase in ODC activity is due, at least in part, to an increase in ODC gene expression and they provide a useful model for the analysis of the molecular effects of UVB radiation.
紫外线辐射在诱发皮肤恶性肿瘤(包括基底细胞癌、鳞状细胞癌和恶性黑色素瘤)中起着重要作用。除了对DNA损伤和修复机制的影响外,紫外线辐射还被证明可调节特定基因的表达,改变其mRNA水平及其相应蛋白质的合成。为了进一步了解紫外线辐射的分子效应,我们研究了鸟氨酸脱羧酶(ODC)基因表达对紫外线B辐射的反应调控。ODC是多胺生物合成中的限速酶,参与生长和分化,并与致癌作用有关。培养的角质形成细胞要么进行假照射,要么暴露于递增剂量的紫外线B(1-5 mJ/cm²)下。在基础条件下对角质形成细胞RNA进行Northern印迹分析,结果显示存在两种ODC mRNA转录本。紫外线B暴露量的增加导致两种ODC mRNA转录本水平呈剂量依赖性增加。紫外线B照射后2小时可观察到ODC基因表达的诱导,并且在紫外线B照射后24小时内ODC mRNA水平持续增加。尽管血清本身具有诱导ODC基因表达的能力,但紫外线B诱导的ODC基因表达增加并不依赖于血清。紫外线B照射后,肌动蛋白和己糖胺酶A的mRNA转录本未被诱导。这些研究表明,紫外线B诱导的ODC活性增加至少部分是由于ODC基因表达的增加,并且它们为分析紫外线B辐射的分子效应提供了一个有用的模型。