Research ReportThe expression and significance of HIF-1α and GLUT-3 in glioma
Introduction
It is well known that malignant tumors are regarded to be in a more or less hypoxic state, with highly malignant tumors being specially hypoxia-resistant (Zhong et al., 1999). Hypoxia-inducible factor-1 (HIF-1), a heterodimer composed of α and β subunit, plays an indispensable role in tumor formation and histogenesis (Semenza, 2002). The expression and transcriptional activity of HIF-1 itself increase when oxygen availability becomes a limiting factor, and several dozen target genes including those involved in glucose transport, glycolysis, and tissue vascularization are acutely transactivated by HIF-1 (Mobasheri et al., 2005). In this process, HIF-1 transcription activity is regulated by the expression level of the HIF-1α subunit (Semenza, 2002), and the loss of the von Hippel-Lindau tumor suppressor gene results in constitutive overexpression of HIF-1α (Huang et al., 1998). In all mammalian cells, one or more of the glucose transporter (GLUT) genes were found. GLUTs, which are integral membrane glycoproteins, play an essential role in facilitating glucose transport. In previous study, Otto Warburg observed that the rate of anaerobic-like glycolysis was increased obviously in malignant tumor cells compared to non-malignant tumor cells or normal tissue cells (Warburg, 1956). GLUT-3 is a representative member of the family and is primarily expressed in neurons. The prominent localization of GLUT-3 to mature neuronal processes suggests an essential role for this transporter in regulating fuel requirements for dendritic and axonal traffic, thereby mediating neurotransmission (Mantych et al., 1992). A variety of researches have shown a close relationship between GLUT-3 and carcinogenesis, tumor development or the unfavorable prognosis of various malignancies (Airley and Mobasheri, 2007, Riedl et al., 2007). However, to our knowledge, none of research about co-expression of HIF-1α and GLUT-3 in human glioma has been found. In this study, we focused primarily on the co-expression of HIF-1α and GLUT-3 on a total of 120 cases of human gliomas and 10 cases of brain tissues by the immunohistochemical method and Western blot with special antibody.
Section snippets
HIF-1α expression was recognized through a nuclear staining of glioma cells mainly
There was no expression of HIF-1α in normal brain tissues. There was statistical significance in the expression of HIF-1α between glioma and normal brain tissues (Z = 2.948, P = 0.003). There was no statistical significance between the expression of HIF-1α and patient' sex and age (P > 0.05). The expression of HIF-1α increased gradually with the increase of pathological grade of glioma (χ2 = 41.401, P < 0.001), and the difference in the expression of HIF-1α in every two groups was significant.
Discussion
Glioma is the most frequent malignant tumor in the brain. Consistent proliferation of tumor cells results in a sharp increase of cell oxygen consumption, which causes anoxic microenvironment. It is known that HIF-1α plays an essential role in adapting the cellular environment to a hypoxic status by inducing the expression of various hypoxia response molecules, including members of GLUT family. Scientists have reported that increased HIF-1α is overexpressed as a result of intratumoral hypoxia,
Case Selection
With institutional review board approval, 120 paraffin-embedded human glioma samples used in this study were obtained from patients admitted to the Department of Neurosurgery, The Third Hospital of Mianyang between 2005 and 2007. A total of 120 patients [61 males, 59 females; ranged from 12 to 70 years old (mean ± standard deviation [SD]: 36.69 ± 13.47)] were included in the study. All the samples of glioma were got at the time of primary tumor excision. All of the 120 glioma samples (grade I, 30
Acknowledgments
We thank Mrs. Ling Sun, Xiaoyan Chen and Juan Li for their assistance in this research. Shaolan Yu and Jicheng Xu are also worth of great thanks for their professional help.
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These authors contributed equally to this work.