GLUT1 gene is a potential hypoxic marker in colorectal cancer patients.

GLUT1 gene is a potential hypoxic marker in colorectal cancer patients.
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DOI:
10.1186/1471-2407-9-241
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发表时间:
2009-07-20
期刊:
影响因子:
3.8
通讯作者:
Lin SR
Lin SR
中科院分区:
医学2区
文献类型:
--
作者:
Chung FY;Huang MY;Yeh CS;Chang HJ;Cheng TL;Yen LC;Wang JY;Lin SR

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肿瘤缺氧是肿瘤对放化疗产生耐药性的重要因素。这项研究调查了结直肠癌细胞在缺氧期间合成的分子,以探索开发能够检测细胞死亡和/或放疗和化疗效率的分子探针的可能性。首先,我们将两种人结直肠腺癌细胞系 SW480(UICC II 期)和 SW620(UICC III 期)细胞在低氧(≤2% O2、93% N2 和 5% CO2)和常氧条件(20% O2、75% N2 和 5% CO2)下孵育 24 小时和 48 小时。 RT-PCR分析低氧条件下GLUT1 mRNA的相对表达率。对从人类结直肠癌患者身上采集的十个癌组织进行了检查。测量HIF-1α和HIF-2α水平以指示缺氧程度,并测定缺氧条件下的基因表达。作为比较,我们测量了 100 名 CRC 患者外周血中的 HIF-1α、HIF-2α 和 GLUT1 水平。缺氧诱导的乳酸在 SW480 细胞中升高 3.24 至 3.36 倍,在 SW620 细胞中升高 3.06 至 3.17 倍。在缺氧条件下,SW620 细胞中 GLUT1 mRNA 增加的相对表达率(升高 1.39 至 1.72 倍)高于 SW480 细胞(升高 1.24 至 1.66 倍)。 CRC 组织标本中 HIF-1α 和 HIF-2α 水平升高,GLUT1 基因显着过表达。 III 期和 IV 期 CRC 组织标本中 GLUT1 升高的比率高于 I 期和 II 期(2.97-4.73 与 1.44-2.11)。与I期患者相比,II期和III期CRC患者外周血中GLUT1 mRNA也有所增加,表明GLUT1可能作为CRC患者的缺氧指标。总之,这项研究证明 GLUT1 有潜力用作分子标记物来指示癌症患者血液中循环的肿瘤所经历的缺氧程度。
Tumor hypoxia is an important factor related to tumor resistance to radiotherapy and chemotherapy. This study investigated molecules synthesized in colorectal cancer cells during hypoxia to explore the possibility of developing molecular probes capable of detecting cell death and/or the efficiency of radiotherapy and chemotherapy. At first, we incubated two human colorectal adenocarcinoma cell lines SW480 (UICC stage II) and SW620 (UICC stage III) cells in hypoxic (≤2% O2, 93% N2, and 5% CO2) and normoxic conditions (20% O2, 75% N2, and 5% CO2) for 24 h and 48 h. The relative expression ratio of GLUT1 mRNA in hypoxic conditions was analyzed by RT-PCR. Ten cancerous tissues collected from human colorectal cancer patients were examined. HIF-1α and HIF-2α levels were measured to indicate the degree of hypoxia, and gene expression under hypoxic conditions was determined. As a comparison, HIF-1α, HIF-2α, and GLUT1 levels were measured in the peripheral blood of 100 CRC patients. Hypoxia-induced lactate was found to be elevated 3.24- to 3.36-fold in SW480 cells, and 3.06- to 3.17-fold in SW620 cells. The increased relative expression ratio of GLUT1 mRNA, under hypoxic conditions was higher in SW620 cells (1.39- to 1.72-fold elevation) than in SW480 cells (1.24- to 1.66-fold elevation). HIF-1α and HIF-2α levels were elevated and GLUT1 genes were significantly overexpressed in CRC tissue specimens. The elevated ratio of GLUT1 was higher in stage III and IV CRC tissue specimens than in the stage I and II (2.97–4.73 versus 1.44–2.11). GLUT1 mRNA was also increased in the peripheral blood of stage II and III CRC patients as compared to stage I patients, suggesting that GLUT1 may serve as a hypoxic indicator in CRC patients. In conclusion, this study demonstrated that GLUT1 has the potential to be employed as a molecular marker to indicate the degree of hypoxia experienced by tumors circulating in the blood of cancer patients.
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