Expression Of HIF-1a And Its Regulating Gene PTEN In Bladder Transitional Cell Carcinoma And Impact Of Them On Tumor Biological Actions

HIF-1 is a hypoxia response regulating factor generally residing in mammalian cells. The regulation of HIF-1 in gene level to VEGF plays a important role in tumor angiogenesis , proliferation and progression. The influencing of some oncogene and anti-oncogene to the expression and activity of HIF-1 determines neoplastic prognosis ultimately.HIF-1 consists of alpha subunit(HIF-1a) and beta subunit(HIF-1 β), HIF-1β is a structional subunit and its expression level in cells is stable; HIF-1a is a functional subunit and not detectable in physiological condition. The level of HIF-1a in cells heighten and take effect on some inducted conditions.Now it has be known that HIF-1a can be activated by many kinds of factors that plays a significant role in cell growth, differentiation and Apoptosis. The influence of oncogene activation and anti-oncogene inactivation have become research emphasis.It was reported that PTEN has regulation effect to HIF-1a as an anti-oncogene.As an important target gene of HIF-1a, VEGF is amajor media of tumor angiogenesis. They influence malignant tumor biology behavior correlately each other. The reaseach about the expression of HIF-la and its relationship with PTE>k VEGF in transitional cell carcinoma of the bladder has a significance to the prognosis and treating regime.In this research ,the expression of HIF-la , PTEN and VEGF was examined in 52 cases of bladder transitional cell carcinoma and 10 normal bladder mucosas by means of immunohistochemical SP technique. The results of immunohistochemical staining were categorized into three grades including(—)(+)(++). The correlation between the expression results and tumor pathological grades, clinical stages, number of lesions were studied.The positive rate of HIF-la was significantly higher in TCC patients(51.9%) than in the normal mucosas(0%). Furthermore, its expression increased with the advance of grade and stage. But there wasn't significantly difference between the primary tumor group or solitary ones and recurrent tumor group or multiple ones.The positive rate of PTEN in TCC group was 71.2%, significantly lower than in nomal mucosas group(100%). And itsexpression had negative correlation with grade and stage.There was no case that observed positive expression of VEGF in 10 cases of normal mucosas ,while the positive rate of VEGF in TCC was 57.7%. And its expression level elevated with the advance of grade and stage, there was statistical significance. The recurrent tumor group had a higher expression level of VEGF than primary tumor group.There were negative correlation both between HIF-la and PTEN and between PTEN and VEGF. Otherwise ,There was positive correlation both between HIF-la and VEGF.These results suggest that HIF-1 as a hypoxia response regulating factor play an important role in angiogenesis , proliferation and progression through regulating VEGF. HIF-la is correlated with pathological grades, clinical stages and the detection of HIF-la expression might be helpful in predicting the biological behavior of bladder transitional cell carcinoma. The tumor suppressor PTEN is a phosphatase. PTEN regulates expression and transcription of HIF-la through PI(3)k/ Akt signal way. The expression of HIF-1 and target gene up-regulate as PI(3)k/ Akt activity increases. In addition, Akt can...