Study On The Role Of HIF-1a In The Pathogenesis Of Condyloma Acuminatum And Its Mechanisms

Part Ⅰ The expression of HIF-la in Condyloma Acuminatum and its SignificanceObjective To study the expression of HIF-la in Condyloma Acuminatum(CA)tissues. Furthermore,to explore its significance and its association with the recurrence of CA patients.Methods The mRNA and protein expression of HIF-la were detected by RT-PCR and immunohistochemistry respectively in30cases of CA and20normal foreskin tissues.Results The positive rates and expression intensity of HIF-la protein were significantly higher in CA than those in normal controls respectively while the positive rates and expression intensity of HIF-la mRNA in CA tissues have no statistical significance compared with those in normal foreskin tissues.Moreover, the expression intensity of HIF-la protein was significantly higher in recurrent CA patients than that in non-recurrent CA patients.Conclusions The hypoxia microenvironment may induce the high expression of HIF-la protein in CA tissues which might play an important role in the pathogenesis of CA while the HIF-la mRNA remains a stable level.The abnormal expression of HIF-la protein was correlated with the prognosis of CA patients and can be used as an index to forecast the recurrence of CA. Part Ⅱ The promotion of CA cells proliferation by HIF-la and its mechanismsObjective To investigate the proliferation activity of CA cells and its association with the recurrence of CA. The expression of GLUT-1was also detected in CA tissues to explore the role of HIF-1a in the promotion of CA cells proliferation and its mechanisms.Methods The mRNA expression of GLUT-1was detected by RT-PCR and the protein expression of GLUT-1and PCNA was detected by immunohistochemistry in30cases of CA and20normal foreskin tissues.Results The positive rates and the number of PI in CA tissues were significantly higher than those in normal controls respectively. Moreover, the positive rates and the number of PI were significantly higher in recurrent CA patients than those in non-recurrent CA patients. The positive rates and expression intensity of GLUT-1mRNA and protein were significantly higher in CA than those in normal controls respectively.The protein expression of HIF-la was both positively correlated with that of GLUT-1and PCNA in CA patients while the protein expression of GLUT-1was also positively correlated with that of PCNA.Conclusions The proliferation activity of CA cells is higher than that of normal foreskin cells which is correlated with the prognosis of CA patients. HIF-1a might combine the HRE of GLUT-1to induce the over-expression of GLUT-1which results in the improvement of the energy metabolism leading to an over-proliferation of CA cells. Part ⅢDetection of microvessel density and study of the role of HIF-la in the angiogenesis in CA tissuesObjective To detect the microvessel density(MVD) in CA tissues and its association with the recurrence of CA and to explore the role of HIF-la in the angiogenesis in CA tissues and its mechanisms.Methods The mRNA expression of VEGF、COX-2、iNOS was detected by RT-PCR and the protein expression of VEGF、COX-2、iNOS and CD34was detected by immunohistochemistry in30cases of CA and20normal foreskin tissues.Results The number of MVD in CA tissues was significantly higher than that in normal controls while the number of MVD in recurrent CA patients was significantly higher than that in non-recurrent CA patients.The positive rates of VEGF mRNA and protein in CA tissues have no statistical significance compared with those in normal foreskin tissues respectively but the expression intensity of VEGF mRNA and protein were significantly higher in CA than those in normal controls respectively.The positive rates and expression intensity of COX-2、 iNOS mRNA and protein were significantly higher in CA than those in normal controls respectively. All of the protein expression of VEGF、COX-2, iNOS were positively correlated with MVD in CA patients while the protein expression of HIF-la was positively correlated with that of VEGF、COX-2、iNOS respectively.Moreover,no correlation was found between the protein expression of VEGF and that of COX-2,nor is that of iNOS.Conclusions The cability of angiogenesis in CA tissues was significantly higher than that in normal controls which is correlated with the prognosis of CA patients.HIF-1a is a central regulating factor in the course of angogenesis which can monitor the angiogenesis in CA tissues by two means:one is the VEGF-dependent route:HIF-la may combine the HRE of VEGF to induce the over-expression of VEGF so as to promote the angiogenesis.The other is the non-VEGF-dependent route:HIF-1a can up-regulate the expression of its target gene such as COX-2and iNOS to favor the angiogenesis...