The Expression And Significance Of The Correlation Factor Of Unfolded Protein Response: XBP1,Bip And VEGF-C In Hepatocarcinoma

Objective: There is a serie of unfavourable factors in the tumorous process of growth,such as hypoxia,innutrition,change of PH,and so on.These status could activate serial cello-stress reaction iter including unfolded protein response(UPR),and have effect on growth of tumor cells.UPR, which is a type of ER stress and one of main iter of signal for ER stress , mean that error folding and unfolding protein couldnot go out from ER according to normal pathway when the normal cells suffer unfavourable conditions that influence protein folding;collect in ER,and activate conductive cascade reaction of signal ,and up-regulate target genetic transcription and down-regulate protein translational level. This kind of cells increases the capability of protein folding and remodel secretion iter through UPR to adapt the growth requirement and the circumstance change. The signal molecules to participate in UPR are Ire1,Bip(GRP78),XBP1,ATF6,VEGF-C and PERK,and so on. XBP1,which is a regulating factor to participate in cell differentiation and also a significant element of UPR composition, promote cell differentiation. VEGF-C is one of main member of VEGF family, which promote the production of blood vessels and lymphatic vessels, participate in neogenesis of blood vessels and lymphatic vessels physiologically and pathologically. Bip, which is a radical factor in UPR signal transmission iter and considered a mark molecule,helps the error folding protein to regain the correct folding mode.Bip,which most studies have focused on,is also the transcriptive target molecule of UPR channel.Untill now,there is no study on adequately analysing UPR activated iter, to evaluate which part of UPR is activated and what degree of that and which kind of tumor cells have experienced ER stress. Hepatocarcinoma is a malignant tumor of liver.Most studies focus on its biological behaviour and its pathogenesis.However,majority of these studies are limited on the relationship between some signal gene and their mechanism in hepatocarcinoma. And few is known about the relationship between more genes and the growth regulation in liver cancer and between the mechanism of genes and clinic symptoms. Few is also known about what degree of UPR activation and how influence the malignant biological behaviour in hepatocarcinoma .So in order to detect the expression of XBP1,Bip and VEGF-C mRNA and protein in hepatocarcinoma tissue by RT-PCR and Western blot, it is dementrated that UPR is activated in process of growth in hepatocarcinoma, and the expression of mRNA and protein is higher than that in normal tissue. And it is approached that the mechanism of action in the growth of hepatocarcinoma,in order to search for a new target for the therapy of hepatocarcinoma. Methods1 Researching the hepatocarcinoma tissue,adjacent hepatic tissue to carcinoma and normal hepatic tissue1.1 To study on the mRNA and protein of XBP1,Bip and VEGF-C in 42 cases of hepatocarcinoma specimen, 15 cases of paired adjacent hepatic tissue to carcinoma and 15 case of normal hepatic tissue using RT-PCR and Western blot. All 42 cases hepatocarcinoma specimen is diagnosed by pathology. The optical density (OD) of the production of RT-PCR is analysed by the software of Gel-proAnalyzer3.1.And to represent the relative amount of gene product ,the ratios of the OD value is calculated between XBP1,Bip,VEGF-C and glyceraldehyde-3- phosphate dehydrogenase (GAPDH).1.2 To authenticate the expression of XBP1 and Bip in protein level by Western Blot in specimen of 57 cases of hepatic tissue. All specimen is diagnosed by pathology.2 Making use of the SAS System for Windows v6.12 software carrying out statistical treatment.Using x±s expressed Test data, comparing different groups using ANOVA. Comparing two groups by T test.α=0.05 as the size of test.When P<0.05,there was the statistical significance. Results1 The expression of XBP1,Bip and VEGF-C mRNA in 72 cases of different hepatic tissue.The expression of XBP1 mRNA in the hepatocarcinoma tissue,adjacent hepatic tissue to carcinoma and normal hepatic tissue is 0.4396±0.0241,0.4152±0.0252 and 0.4095±0.0149 respectively. The expression of XBP1 mRNA is higher in hepatocarcinoma than in the others(P<0.05).The expression of VEGF-C mRNA in the hepatocarcinoma tissue,adjacent hepatic tissue to carcinoma and normal hepatic tissue is 0.4447±0.0335,0.4195±0.0334 and 0.4019±0.0259 respectively. The expression of VEGF-C mRNA is higher in hepatocarcinoma than in the others (P<0.05). The expression of Bip mRNA in the hepatocarcinoma tissue,adjacent hepatic tissue to carcinoma and normal hepatic tissue is 0.4772±0.0401,0.4332±0.0488 and 0.4301±0.0398 respectively; the expression of Bip mRNA is higher in hepatocarcinoma than in the others(P<0.05).2 The expression of protein of XBP1 and Bip in the hepatocarcinoma tissue and normal hepatic tissue.The experiment indicates:the two kinds of protein all expresses in the hepatocarcinoma tissue and normal hepatic tissue, but they are higher in hepatocarcinoma than in the normal .Conclusion1 It is existed that unfold protein response(UPR) is activated in the growth process of hepatocarcinoma.2 The expression of XBP1,Bip and VEGF-C protein was accordant with their mRNA,and all of them are higher in the hepatocarcinoma tissue than in the normal hepatic tissue. It is possible that the changes of these genes and protein have relationship with the carcinogenesis ,growth and metastases of hepatocarcinoma,and might affect on molecular mechanism of hepatoma significantly.It is also descripted that unfold protein response may have very important role in the pocess of carcinogenesis.