Shinozaki Hiroharu, Yang Kan, Fan Kunhua, Edelmann Winfried, Kucherlapati Raju, Weinstein I Bernard, Lipkin Martin
Strang Cancer Prevention Center, New York, NY 10021, USA.
Anticancer Res. 2003 May-Jun;23(3B):2217-26.
Altered expression of cyclin D1 contributes to the development of several types of cancer, including colorectal cancer. This study examined cyclin D1 expression in 32 intestinal tumors in different stages of tumorigenesis in Apc1638N mice, a mouse model for human familial adenomatous polyposis (FAP). Three morphological patterns of expression of cyclin D1 in intestinal epithelial cells were found: nuclear, punctate-cytoplasmic and fine granular cytoplasmic. The nuclear pattern of cyclin D1 was detected in all of the tumors, including adenomas (n = 18) and adenocarcinomas (n = 14); this pattern was found predominantly in the tubular region of the tumors and in flat mucosa adjacent to a subset of the tumors (67% of adenomas and 57% of carcinomas). The punctate-cytoplasmic pattern of cyclin D1 expression was found in all adenocarcinomas and a majority of adenomas (80%), mainly in invasive and villous areas of the tumors; it was not found in normal flat adjacent mucosa suggesting that this pattern and altered cytoplasmic/nuclear expression were associated with tumor progression. Fine cytoplasmic granules were located in normal duodenum in the basal portion of the crypts and in colon in epithelial cells at the surface of the colonic crypts; in both duodenum and colon the number of cells with fine cytoplasmic granules significantly increased after feeding a Western-style diet. These altered patterns of expression of cyclin D1 may provide useful biomarkers of abnormal cell development for studies of tumorigenesis and the effects of chemopreventive agents.
细胞周期蛋白D1表达的改变促成了包括结直肠癌在内的多种癌症的发展。本研究检测了Apc1638N小鼠（一种人类家族性腺瘤性息肉病（FAP）的小鼠模型）肿瘤发生不同阶段的32个肠道肿瘤中细胞周期蛋白D1的表达。在肠上皮细胞中发现了细胞周期蛋白D1的三种形态学表达模式：核型、点状胞质型和细颗粒胞质型。在所有肿瘤中均检测到细胞周期蛋白D1的核型模式，包括腺瘤（n = 18）和腺癌（n = 14）；这种模式主要见于肿瘤的管状区域以及部分肿瘤相邻的扁平黏膜（67%的腺瘤和57%的癌）。细胞周期蛋白D1表达的点状胞质型模式见于所有腺癌和大多数腺瘤（80%），主要在肿瘤的浸润和绒毛区域；在相邻的正常扁平黏膜中未发现，这表明这种模式以及胞质/核表达的改变与肿瘤进展相关。细胞质颗粒位于正常十二指肠隐窝底部以及结肠隐窝表面的上皮细胞中；在十二指肠和结肠中，喂食西式饮食后，具有细胞质颗粒的细胞数量均显著增加。细胞周期蛋白D1这些表达模式的改变可能为肿瘤发生及化学预防剂作用的研究提供有用的异常细胞发育生物标志物。
