Arnoletti J P, Upson J, Babb J S, Bellacosa A, Watson J C
Dept. of Surgery, Section of Surgical Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
J Exp Clin Cancer Res. 2005 Jun;24(2):279-87.
The purpose of the following study is to describe the localization of COX-2 protein and COX-2 mRNA during human colorectal tumorigenesis and to identify potential cellular targets for COX-2 inhibition in chemopreventive strategies. Immunohistochemistry with digital image analysis was used to determine COX-2 protein expression in histologic sections containing synchronous normal colorectal mucosa, adenomas and carcinomas, from 17 previously untreated patients. Epithelial and stromal COX-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), on laser-capture microdissected samples from the same histologies. The stromal compartment in normal colorectal mucosa and adenomas showed higher levels of COX-2 protein expression compared to colorectal carcinomas (p < .0001). Conversely, epithelial COX-2 protein was significantly increased only after development of the invasive phenotype (p < .0001). RT-PCR demonstrated higher stromal COX-2 mRNA expression compared to that within the epithelium for colorectal adenomas and carcinomas. In conclusion, stromal COX-2 may be the target for chemopreventive agents in the early stages of colorectal carcinogenesis.
以下研究的目的是描述COX - 2蛋白和COX - 2 mRNA在人类结直肠癌发生过程中的定位，并确定在化学预防策略中COX - 2抑制的潜在细胞靶点。对17例未经治疗的患者，采用免疫组织化学结合数字图像分析来确定COX - 2蛋白在含有同步正常结直肠黏膜、腺瘤和癌的组织切片中的表达。通过逆转录 - 聚合酶链反应（RT - PCR）分析来自相同组织学类型的激光捕获显微切割样本中的上皮和基质COX - 2 mRNA表达。与结直肠癌相比，正常结直肠黏膜和腺瘤中的基质部分显示出更高水平的COX - 2蛋白表达（p <.0001）。相反，上皮COX - 2蛋白仅在侵袭性表型出现后才显著增加（p <.0001）。RT - PCR显示，与结直肠腺瘤和癌上皮内的COX - 2 mRNA表达相比，基质中的表达更高。总之，基质COX - 2可能是结直肠癌发生早期化学预防药物的靶点。
