Colorectal tumorigenesis involves the development of aberrant crypt foci (ACF) or preneoplastic lesions, representing the earliest morphological lesion visible in colon cancer. The purpose of this study was to determine changes in protein expression in carcinogen-induced ACF as they mature and transform into adenomas. Protein expression profiles of azoxymethane (AOM)-induced F344 rat colon ACF and adenomas were compared at four time points, 4 (control), 8, 16, and 24 weeks post AOM administration (n= 9/group), with time points correlating with induction and transformation events. At each time point, micro-dissected ACF and/or adenoma tissues were analyzed across multiple quantitative two-dimensional (2D-DIGE) gels using a Cy-dye labeling technique and a pooled internal standard to quantify expression changes with statistical confidence. Western blot and subsequent network pathway mapping were used to confirm and elucidate differentially expressed (p≤ 0.05) proteins, including changes in vinculin (Vcl;p= 0.007), scinderin (Scin;p= 0.02), and profilin (Pfn1;p= 0.01), By determining protein expression changes in ACF as they mature and transform into adenomas, a “baseline” of altered regulatory proteins associated with adenocarcinoma development in this model has been elucidated. These data will enable future studies aimed at biomarker identification and understanding the molecular biology of intestinal tumorigenesis and adenocarcinoma maturation under varying intestinal conditions.
结直肠肿瘤发生涉及异常隐窝病灶（ACF）或癌前病变的发展，这是结肠癌中可见的最早期形态学病变。本研究旨在确定致癌物诱导的ACF在成熟并转化为腺瘤过程中蛋白质表达的变化。通过比较氧化偶氮甲烷（AOM）诱导的F344大鼠结肠ACF和腺瘤在四个时间点（AOM给药后4周（对照组）、8周、16周和24周，每组n=9）的蛋白质表达谱，这些时间点与诱导和转化事件相关。在每个时间点，采用Cy染料标记技术和混合内标，通过多重定量二维凝胶电泳（2D-DIGE）分析显微切割的ACF和/或腺瘤组织，以统计学置信度量化表达变化。Western印迹及后续网络通路图谱分析用于确认和阐明差异表达（p≤0.05）的蛋白质，包括纽蛋白（Vcl；p=0.007）、肌切蛋白（Scin；p=0.02）和丝切蛋白（Pfn1；p=0.01）的变化。通过确定ACF在成熟和转化为腺瘤过程中的蛋白质表达变化，本研究阐明了该模型中与腺癌发展相关的调控蛋白改变的“基线”。这些数据将为未来研究提供基础，旨在识别生物标志物，并理解不同肠道条件下肠道肿瘤发生和腺癌成熟的分子生物学机制。
肿瘤(癌症)患者之家