Izawa Hikaru, Yamamoto Hirofumi, Ikeda Masataka, Ikeda Kimimasa, Fukunaga Hiroki, Yasui Masayoshi, Ikenaga Masakazu, Sekimoto Mitsugu, Monden Takushi, Matsuura Nariaki, Monden Morito
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Oncol Rep. 2002 Nov-Dec;9(6):1313-8.
Overexpression or amplification of G1 cyclins has been demonstrated in various types of human cancers. Overexpression of cyclin D1, an accelerator of cell cycle, is thought to be an early event in colonic multistage carcinogenesis, but its expression at transformation from benign to neoplastic foci is not clear. We analyzed the expression of cyclin D1 and its catalystic partner CDK4 in colon polyps containing neoplastic foci. For direct comparison of the expression in adenomatous tissues and neoplastic foci, proteins in adequate amounts were extracted from paraffin embedded sections. Western blot and densitometry analyses showed that cyclin D1 expression was 2.3-times and 2.5-times higher in adenomatous tissues and neoplastic foci, compared with normal colonic mucosa. In contrast, the levels of CDK4 and CDK2 expression were only modestly increased in adenomatous tissues but significantly higher in neoplastic foci, relative to normal mucosa. Expression of PCNA, a cell proliferation marker, increased from normal mucosa to adenoma to focal cancer. Our findings suggest that overexpression of cyclin D1 may be associated with high proliferative activity in adenomatous tissues and that concurrent high expression of cyclin D1 and CDK4 may further perturb cell cycle progression and play a pivotal role in colonic carcinogenesis.
在各类人类癌症中均已证实存在G1细胞周期蛋白的过表达或扩增。细胞周期加速器细胞周期蛋白D1的过表达被认为是结肠多阶段致癌过程中的早期事件,但其在从良性病灶向肿瘤病灶转变过程中的表达情况尚不清楚。我们分析了含有肿瘤病灶的结肠息肉中细胞周期蛋白D1及其催化伴侣CDK4的表达情况。为了直接比较腺瘤组织和肿瘤病灶中的表达,从石蜡包埋切片中提取了足量的蛋白质。蛋白质印迹法和光密度分析表明,与正常结肠黏膜相比,腺瘤组织和肿瘤病灶中细胞周期蛋白D1的表达分别高出2.3倍和2.5倍。相比之下,相对于正常黏膜,CDK4和CDK2在腺瘤组织中的表达水平仅适度增加,但在肿瘤病灶中显著升高。细胞增殖标志物PCNA的表达从正常黏膜到腺瘤再到局灶性癌逐渐增加。我们的研究结果表明,细胞周期蛋白D1的过表达可能与腺瘤组织中的高增殖活性相关,并且细胞周期蛋白D1和CDK4的同时高表达可能会进一步扰乱细胞周期进程,并在结肠癌发生过程中起关键作用。