Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas
Concerted overexpression of the genes encoding p21 and cyclin D1 is associated with growth inhibition and differentiation in various carcinomas
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DOI：
10.1136/mp.52.2.78
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发表时间：
1999-04-01
期刊：
影响因子：
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通讯作者：
Baak, JPA
中科院分区：
文献类型：
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作者：
de Jong, JS;van Diest, PJ;Baak, JPA
目的：应用免疫组织化学和免疫荧光双重染色方法，检测Ki67抗体检测的细胞周期蛋白d1和p21基因在增殖期和非增殖期细胞中的表达，并探讨其与分化程度的关系。结果免疫荧光双重染色显示，在头颈部鳞状细胞癌中Ki67抗原、细胞周期蛋白D1和p21的表达呈分化相关梯度：Ki67在肿瘤的基底层表达，细胞周期蛋白D1和p21基因在肿瘤分化程度较高的层共表达。乳腺癌和卵巢癌的细胞通常共表达p21和细胞周期蛋白d1基因，而细胞周期蛋白d1和Ki67基因不共表达。对MCF7乳腺癌细胞的Western印迹分析表明，当细胞周期蛋白D1基因表达被诱导时，p21的表达上调。结论：细胞周期蛋白D1基因的过表达可能通过诱导细胞周期蛋白D1诱导p21的表达而导致多种人类肿瘤的生长停滞。在鳞状细胞中。癌组织中，编码细胞周期蛋白d1和p21的基因协同过表达也可能诱导分化。
Aims-To investigate the expression of the genes encoding cyclin D1 and p21 in proliferative and non-proliferative cells, as demonstrated by the Ki67 antibody, and to correlate these findings with differentiation.Methods-Immunohistochemistry and immunofluorescence double staining were performed on three breast cancers, two squamous cell cancers of the head and neck, and one ovarium cystadenocarcinoma. In addition, the in vitro effect of cyclin D1 on p21 gene expression in MCF7 breast cancer cells was evaluated.Results-Immunofluorescence double staining showed a differentiation related gradient in the detection of the Ki67 antigen, cyclin D1, and p21 in squamous cell cancers of the head and neck: Ki67 was detected in the basal layers of the tumour and the cyclin D1 and p21 genes were coexpressed in the higher, more differentiated layers of the tumour. The breast and ovarian cancers often had cells that coexpressed the p21 and cyclin D1 genes, whereas coexpression of cyclin D1 and Ki67 did not occur. Western blot analysis of the MCF7 breast cancer cells showed an upregulation of p21 production when cyclin D1 gene expression was induced.Conclusion-Overexpression of the cyclin D1 gene seems to lead to growth arrest in a variety of human cancers, possibly through the induction of p21 by cyclin D1. In squamous cell. cancer, concerted overexpression of the genes encoding cyclin D1 and p21 might also induce differentiation.