Wincewicz Andrzej, Sulkowska Mariola, Koda Mariusz, Kanczuga-Koda Luiza, Witkowska Ewa, Sulkowski Stanislaw
Departments of General and Clinical Pathomorphology, Medical University of Bialystok, Waszyngtona St. 13, 15-269 Bialystok, Poland.
Ann N Y Acad Sci. 2007 Jan;1095:53-61. doi: 10.1196/annals.1397.007.
Hypoxic cancer cells overexpress Glucose transporter 1 (GLUT-1) to accelerate glucose intake mainly for low effective, anaerobic respiration, so that they would not die of oxygen deficiency. Ischemic cell injury triggers apoptosis. Regulators of cell suicide like Bax and Bcl-xL combine their functions to cause apoptosis or to rescue cells from death. GLUT-1, Bax, and Bcl-xL are of prognostic significance in colorectal cancer but they have not been compared, yet. Thus, we aimed to determine eventual correlations between GLUT-1, Bax, and Bcl-xL in association with different clinicopathological features of colorectal cancer patients. Expressions of the proteins were evaluated in specimens of 150 colorectal patients by immunohistochemistry. The levels of tissue expressions were statistically analyzed with Spearman's correlation test. As in group of all the patients, GLUT-1 matched Bcl-xL and Bax in statistically significant manner regardless of different node status, grade of histological differentiation, histopathological type, tumor site, gender and age of patients. GLUT-1 correlated highly with Bcl-xL in both groups of various tumor growth extent: pT1 + pT2 and pT3 + pT4 tumors (P < 0.016, r = 0.6340, P < 0.0001, r = 0.5204, respectively). Bax correlated with GLUT-1 (P < 0.0001, r = 0.4284) and Bcl-xL (P < 0.0001, r = 0.5233) in pT3 and pT4 tumors without any statistical significance in a homologous comparison at pT1 and pT2 stage (P > 0.173, r = 0.1078, P > 0.744, r = 0.1, respectively). Significant coexpression of GLUT-1, Bcl-xL, and Bax could point to cooperation of these regulatory proteins in elimination due to irreversible injury, adaptation to hypoxia, reduction of further damage, and survival of colorectal cancer cells.
缺氧癌细胞过度表达葡萄糖转运蛋白1（GLUT-1）以加速葡萄糖摄取，主要用于低效的无氧呼吸，从而避免因缺氧而死亡。缺血性细胞损伤会引发细胞凋亡。细胞自杀调节因子如Bax和Bcl-xL共同发挥作用，导致细胞凋亡或使细胞免于死亡。GLUT-1、Bax和Bcl-xL在结直肠癌中具有预后意义，但尚未进行比较。因此，我们旨在确定GLUT-1、Bax和Bcl-xL与结直肠癌患者不同临床病理特征之间的最终相关性。通过免疫组织化学评估150例结直肠癌患者标本中这些蛋白的表达。用Spearman相关性检验对组织表达水平进行统计学分析。在所有患者组中，无论患者的淋巴结状态、组织学分化程度、组织病理学类型、肿瘤部位、性别和年龄如何，GLUT-1与Bcl-xL和Bax均呈统计学显著相关。在不同肿瘤生长范围的两组中，GLUT-1与Bcl-xL均高度相关：pT1 + pT2和pT3 + pT4肿瘤（分别为P < 0.016，r = 0.6340；P < 0.0001，r = 0.5204）。在pT3和pT4肿瘤中，Bax与GLUT-1（P < 0.0001，r = 0.4284）和Bcl-xL（P < 0.0001，r = 0.5233）相关，而在pT1和pT2阶段的同源比较中无统计学意义（分别为P > 0.173，r = 0.1078；P > 0.744，r = 0.1）。GLUT-1、Bcl-xL和Bax的显著共表达可能表明这些调节蛋白在结直肠癌细胞因不可逆损伤而清除、适应缺氧、减少进一步损伤和存活过程中存在协同作用。
