Shin Jeong Eun, Jung Sung-Ae, Kim Seong-Eun, Joo Yang-Hee, Shim Ki-Nam, Kim Tae Hun, Yoo Kwon, Moon Il-Hwan
Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
Korean J Gastroenterol. 2007 Jul;50(1):9-18.
BACKGROUND/AIMS: This study was aimed to investigate the expression of matrix metalloproteinase-2 (MMP-2), hypoxia-inducible factor (HIF)-1alpha, and vascular endothelial growth factor (VEGF) in colonic adenoma-carcinoma sequence.
Thirty-two tissue samples of colon adenoma, 11 of early colon cancer and 36 of advanced colon cancer were collected by colonoscopic biopsy. Normal colonic tissues were also collected from the same subjects. The mRNA expression levels of MMP-2, HIF-1alpha, and VEGF were quantitated using semiquantitative reverse transcription polymerase chain reactions. The protein expressions of activated MMP-2 and HIF-1alpha were examined by gelatin zymography and by Western blot in surgically resected cases, respectively.
The expression level of MMP-2 mRNA showed a progressive increase in the advance of the colorectal adenoma-carcinoma sequence (p<0.05). In colon cancer tissues, the expression level of MMP-2 mRNA showed an increasing trend according to differentiation, lymphatic invasion and Dukes' stage (p<0.05). The protein expression of activated MMP-2 was observed in 10 of 11 (91%) cases of cancer tissues. The mRNA expression levels of HIF-1alpha and VEGF were greater in tissues of early and advanced colon cancer compared with colon adenoma (p<0.05; p<0.001). The protein expression of HIF-1alpha was observed in 9 of 11 (82%) cases of cancer tissues. The mRNA expression level of HIF-1alpha showed a positive correlation with MMP-2 and VEGF, respectively (r=0.52, p<0.001; r=0.76, p<0.001).
MMP-2, HIF-1alpha, and VEGF may be useful in detecting early carcinogenesis and progression of colon cancer.
背景/目的：本研究旨在调查基质金属蛋白酶-2（MMP-2）、缺氧诱导因子（HIF）-1α和血管内皮生长因子（VEGF）在结肠腺瘤-癌序列中的表达情况。
通过结肠镜活检收集32例结肠腺瘤组织样本、11例早期结肠癌组织样本和36例进展期结肠癌组织样本。同时从同一受试者身上收集正常结肠组织。采用半定量逆转录聚合酶链反应定量检测MMP-2、HIF-1α和VEGF的mRNA表达水平。分别通过明胶酶谱法和蛋白质印迹法检测手术切除病例中活化MMP-2和HIF-1α的蛋白表达。
MMP-2 mRNA的表达水平在结直肠腺瘤-癌序列进展过程中呈逐渐升高趋势（p<0.05）。在结肠癌组织中，MMP-2 mRNA的表达水平根据分化程度、淋巴浸润和Dukes分期呈上升趋势（p<0.05）。在11例癌组织中有10例（91%）观察到活化MMP-2的蛋白表达。与结肠腺瘤相比，早期和进展期结肠癌组织中HIF-1α和VEGF的mRNA表达水平更高（p<0.05；p<0.001）。在11例癌组织中有9例（82%）观察到HIF-1α的蛋白表达。HIF-1α的mRNA表达水平分别与MMP-2和VEGF呈正相关（r=0.52，p<0.001；r=0.76，p<0.001）。
MMP-2、HIF-1α和VEGF可能有助于检测结肠癌的早期癌变和进展。
