Nürnberg W, Artuc M, Nawrath M, Lovric J, Stüting S, Moelling K, Czarnetzki B M, Schadendorf D
Department of Dermatology, Virchow-Klinikum, Humboldt-Universität zu Berlin, Germany.
Cancer Res. 1995 Oct 1;55(19):4432-7.
Human c-myb is normally involved in the regulation of proliferation and differentiation of hematopoietic cells. Until now, only a few reports have described elevated c-myb gene expression in epithelial tissue, suggesting that under certain circumstances, c-Myb protein might play a role during the process of malignant transformation of epithelial cells. To investigate a possible role of c-myb during papillomavirus-associated carcinogenesis, we investigated the c-myb mRNA expression in human papillomavirus (HPV)-associated tumors and tumor cell lines. Seven of nine cervical carcinomas and two of three carcinoma cell lines exhibited elevated c-myb transcriptional activity. In contrast to malignant cervical neoplasias, only 3 of 15 condylomata acuminata expressed a sparse signal for c-myb mRNA. Since the c-Myb protein has been described as a potent transcriptional regulator, we investigated the transactivating properties of c-Myb on the HPV-16 promoter/enhancer. Cotransfection of a chloramphenicol acetyltransferase-reporter plasmid containing the HPV-16 enhancer/promoter element with a full-length c-Myb-expressing plasmid resulted in a significant induction (4.3-fold) of the HPV-16 promoter, whereas expression of a carboxy-terminally deleted c-Myb protein led to no effects. Gel shift experiments showed a specific binding of recombinant c-Myb protein on the HPV-16 P97 enhancer. These data indicate that elevated c-myb expression occurs with HPV-associated cell transformation. Since c-Myb has been shown to stimulate the HPV-derived oncoprotein expression via transcriptional activation, it may play a role in the process of HPV-associated cervical carcinogenesis.
人c-myb通常参与造血细胞增殖和分化的调控。到目前为止，仅有少数报道描述了上皮组织中c-myb基因表达升高，这表明在某些情况下，c-Myb蛋白可能在上皮细胞恶性转化过程中发挥作用。为了研究c-myb在乳头瘤病毒相关致癌过程中可能发挥的作用，我们检测了人乳头瘤病毒（HPV）相关肿瘤及肿瘤细胞系中c-myb mRNA的表达。9例宫颈癌中的7例以及3种癌细胞系中的2种呈现出c-myb转录活性升高。与宫颈恶性肿瘤不同，15例尖锐湿疣中只有3例c-myb mRNA表达呈微弱信号。由于c-Myb蛋白被描述为一种有效的转录调节因子，我们研究了c-Myb对HPV-16启动子/增强子的反式激活特性。将含有HPV-16增强子/启动子元件的氯霉素乙酰转移酶报告质粒与全长c-Myb表达质粒共转染，导致HPV-16启动子显著诱导（4.3倍），而羧基末端缺失的c-Myb蛋白表达则无此效应。凝胶迁移实验显示重组c-Myb蛋白与HPV-16 P97增强子特异性结合。这些数据表明，c-myb表达升高与HPV相关的细胞转化有关。由于c-Myb已被证明可通过转录激活刺激HPV衍生的癌蛋白表达，它可能在HPV相关的宫颈癌发生过程中发挥作用。
