Robles A I, Conti C J
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957-0389, USA.
Carcinogenesis. 1995 Apr;16(4):781-6. doi: 10.1093/carcin/16.4.781.
Abnormal expression of cell-cycle regulatory proteins, particularly cyclin D1, has been described in human cancers. However, there are few reports of this kind in experimental carcinogenesis models, which provide a framework to analyze the importance of those alterations in early cancer development. Previous studies from our laboratory showed that cyclin D1 mRNA was overexpressed in skin tumors generated in SENCAR mice by a two-stage carcinogenesis protocol. In the study presented here, immunoprecipitation of fresh tumor samples confirmed the overexpression of cyclin D1 protein. We also developed an immunohistochemical technique to determine which cells in the lesions overexpressed the cyclin and the timing of deregulation during cancer development. Surprisingly, we found that all premalignant lesions, including small incipient papillomas, overexpressed cyclin D1, whereas normal and hyperproliferative skin were negative. Nuclear immunostaining was detected only in the proliferative compartments of the tumors and showed an apparent cell-cycle-related variation. These results provide evidence for a role of cyclin D1 overexpression in mouse skin carcinogenesis and support the use of this model as an alternative to in vitro studies to help understand the involvement of cyclin deregulation in cancer development.
细胞周期调节蛋白的异常表达，尤其是细胞周期蛋白D1，已在人类癌症中有所描述。然而，在实验性致癌模型中这类报道很少，而实验性致癌模型为分析这些改变在癌症早期发展中的重要性提供了一个框架。我们实验室之前的研究表明，在通过两阶段致癌方案在SENCAR小鼠中产生的皮肤肿瘤中，细胞周期蛋白D1信使核糖核酸（mRNA）过表达。在本文所呈现的研究中，对新鲜肿瘤样本进行免疫沉淀证实了细胞周期蛋白D1蛋白的过表达。我们还开发了一种免疫组织化学技术，以确定病变中的哪些细胞过表达该细胞周期蛋白以及在癌症发展过程中失调的时间。令人惊讶的是，我们发现所有癌前病变，包括小的早期乳头状瘤，均过表达细胞周期蛋白D1，而正常皮肤和增殖性皮肤呈阴性。核免疫染色仅在肿瘤的增殖区检测到，并显示出明显的与细胞周期相关的变化。这些结果为细胞周期蛋白D1过表达在小鼠皮肤癌发生中的作用提供了证据，并支持使用该模型作为体外研究的替代方法，以帮助理解细胞周期蛋白失调在癌症发展中的作用。
