Sinicrope F A, Ruan S B, Cleary K R, Stephens L C, Lee J J, Levin B
Department of Gastrointestinal Medical Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1995 Jan 15;55(2):237-41.
Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.
细胞凋亡或程序性细胞死亡是一种机制，通过该机制，具有DNA损伤的细胞可以被清除。bcl-2原癌基因是一种已知的细胞凋亡抑制剂，它可能会使含有基因改变的细胞积累和增殖。为了确定bcl-2基因在结直肠癌发生过程中是否以及何时被激活，以及它与p53的关系，我们使用免疫组织化学分析了正常黏膜、增生性和发育异常的上皮息肉以及癌组织中这些标志物的表达。在正常和增生性黏膜中，bcl-2染色仅限于基底上皮细胞，而在发育异常的息肉和癌组织中，bcl-2表达则在基底旁和表层区域被检测到。在腺瘤中，发现bcl-2和p53表达呈负相关，这表明这些标志物可能调节共同的细胞死亡途径。此外，经组织学测定，bcl-2阳性细胞比例高的癌组织比bcl-2表达低或无表达的癌组织更有可能具有低自发凋亡率。bcl-2基因的异常激活似乎是结直肠癌发生过程中的一个早期事件，它可以在体内抑制细胞凋亡，并可能促进肿瘤进展。
