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The Expression Of HIF-1α And GLUT1in Renal Cell Carcinoma And Its Clinical Implications

Posted on:2014-11-29Degree:MasterType:Thesis
Country:ChinaCandidate:J J PengFull Text:PDF
GTID:2254330392467499Subject:Surgery
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ObjectiveTo analyse preliminary the protein expression of hypoxia induciblefactor-1α (HIF-1α) and Glucose transporter-1(GLUT1) in clear cell RCC. Expandingthe number of cases, further evaluate its clinical implications. Methods Western blotwas applied to detect the differential protein levels of HIF-1α and GLUT1in tumortissues and corresponding macroscopically normal kidney tissues within eight patients.All,the,eight,RCC,samples,are,clear,cell,RCC,subtype.Collected,samples,46,of,surgical,resection,of,renal,cell,carcinoma,specimens,as,the,experimental,group,,and,the,other,35,cases,of,para-tumor,,kidney,,tissue,,as,,the,control,,group.,Use,,the,,method,,of,,Immunohistochemical to detect the expression of HIF-1α and GLUT1, and collectedclinical data to study the relationship between their expression levels andcharacteristics of renal carcinogenesis. Results1, Western blot displayed adramatically increased HIF-1α and GLUT1protein content in cancerous samples thanin normal kidney tissues.2, HIF-1α expression in renal cell tumor (28/46) is higherthan normal kidney tissues (4/35) next to the cancer, the difference was statisticallysignificant (P<0.05); GLUT1in renal cell carcinoma (34/46) is higher than in thecancer adjacent normal renal tissue (9/35), the difference was statistically significant(P<0.05). There was no statistically significant associations between HIF-1αexpression and gender and age (P﹥0.05), whereas HIF-1α had correlation withclinicopathological variables and nuclear grade(P<0.05). By contrast, there was nosignificant between GLUT1and gender and age, TNM stage and nuclear grade (P﹥0.05). GLUT1correlated significantly (r=0.621, P<0.01) with HIF-1α. Conclusion HIF-1α and GLUT1have different levels of elevated expressed in RCC. Highexpression levels of HIF-1α and GLUT1may play a important role in RCCdevelopment. There were correlation between the expression of HIF-1α and GLUT1and the clinicopathlogical factors of RCC. Furthermore, heavy levels of HIF-1α andGLUT1made a difference in clear cell RCC growth and progression cooperatively.Objective To investigate the changes in the expression of hypoxia inducible factor-1α(HIF-1α) and Glucose transporter-1(GLUT1) in RCC786-0cells under differenthypoxia phases and its clinical implications.Methods786-0cells were cultured underlow oxygen tension for different phases (8,16and24hour). The mRNA and proteinexpressions of HIF-1α and GLUT1in786-0cells were detected by reversetranscription-polymerase chain reaction analysis (RT-PCR) and Western blot analysisrespectively. Results Few of mRNA and protein expression of HIF-1α and GLUT1could observed in RCC786-0cells under normal culture condition. After the hypoxiatreatment (8,16and24hours), the protein expression of HIF-1α and GLUT1wasdramatically increased with correspondence to the different hypoxia time (P <0.01).The mRNA level of HIF-1α changed significantly (P <0.05), while the mRNA levelof GLUT1showed no statistically significant (P>0.05).Conclusion The expressionof HIF-1α and GLUT1in786-0cells was elevated under hypoxia. The regulation ofHIF-1α changed both on the translation and transcription level, while GLUT1in RCCmay be on the translation level instead of transcription level under the differenthypoxia conditions. It suggest that controlling the protein expression of GLUT1maybe a method to suppress the growth of RCC.
Keywords/Search Tags:renal cell carcinoma, hypoxia inducible factor-1α (HIF-1α), Glucosetransporter-1(GLUT1), hypoxia culture, RCC786-0cells
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