Expression Of Hypoxia-inducible Factors And Its Related Proteins In Hepatoblastoma

【Objective】The transcription factor hypoxia-inducible factor is a key regulator responsible for the induction of genes that facilitate adaptation and survival of cells and the whole organism from normoxia to hypoxia.HIF is anα/βheterodimer that binds hypoxia response elements(HREs) at target gene loci under hypoxic conditions.There are three subtypes of HIFs:HIF-1,HIF-2,and HIF-3.HIF-1 and HIF-2 have been proved to be important to the growth of tumors.The hypoxic condition helps HIF-αsubunit escape proteolysis,dimerize with HIF-1β,recruit coactivators,and activate transcription via HREs.Moreover,some kinds of oncogenes,cytokines and chemical substances can also have effects on the expression of HIF selectively or simultaneously.HIF acts as a key regulator responsible for the adaptation in hypoxic conditions of tumors,which has been proved in many studies in the world.HIF can also promote the growth of tumors by regulating the expression of some kinds of cytokines, such as vascular endothelial growth factor,glucose transporter-1 and transforming growth factor-α,etc..These cytokines are also proved to be helpful for the growth and the metabasis of tumors.Hepatoblastoma,the most common primary liver malignancy in childhood,is known as a kind of tumor with fast growth and high malignancy grade.If HIFs have effects on the growth of hepatoblastoma is still unknown.In our experiment,the expression of HIF-1α,HIF-2α,VEGF,GLUT-1 and TGF-αin hepatoblastoma was detected by immunohistochemical techniques in order to find out if HIFs play a role in the growth of hepatoblastoma.【Methods】Three groups of pathological specimens were chosen in the experiment.The tumor group contained 30 specimens of hepatoblastoma tissue from the patients who admitted in our hospital during the past eleven years.The first control group contained 30 specimens of liver tissue which located more than 5 cm far away from the borderline of the hepatoblastoma.The second control group contained 30 specimens of liver tissue from biliary atresia patients who also admitted in during the past eleven years.The PRETEXT system can accurately describe the maliganacy grade of hepatoblastoma and can be used to estimate the prognosis.Therefore,the tumor group were furtherly divided into two groups according to the PRETEXT:the low group(PRETEXTⅠ,Ⅱ) and the high group(PRETEXTⅢ,Ⅳ).Hypoxia-inducible factor 1-alpha,hypoxia-inducible factor 2-alpha,vascular endothelial growth factor, glucose transporter-1,transforming growth factor-alpha were detected in the specimens by immtmohistochemical techniques.Images were analyzed by computer image processing system,and datas were statistically compared by t test.【Results】The positive expression of the five kinds of proteins is expressed as brown granules in cytoplasm.These five kinds of proteins all express higher in the specimens of the tumor group than the other two groups.HIF-2α,VEGF,GLUT-1 express higher in the specimens of the first control group than the second control group.HIF-1α,TGF-αexpress higher in the specimens of the high group than the low group.【Conclusions】1.The five kinds of proteins detected in the experiment all have high expression in hepatoblastoma.It shows that hypoxia-inducible factors can play a role in the growth of hepatoblastoma.2.HIF-1αand TGF-αmay have effect in the prognosis of hepatoblastoma.