Study Of Expressions Of Caveolin-1, Cyclin D1 And E-cadherin In Renal Cell Carcinoma

Background:Caveolae are specialized lipid raft microdomains forming 50 to 100 nm flask-shaped vesicular invaginations of the plasma membrane,which serve as a scaffold for signaling molecules related to cell adhesion,growth and survival.It is functionally and structurally highly conserved.To date the mammalian caveolin family consists of the 4 proteins-caveolin-1α,1β,2 and 3,which encoded by 3 genes. Caveolin-1 has been shown to be involved in the regulation of numerous signaling cascades.The gene caveolin-1 has been shown to be a metastasis related gene. Increased caveolin-1 expression has been reported to be associated with shortened progression-free survival and lymph node metastasis.On the other hand,caveolin-1 has been implicated in the inhibition of cancer progression.Thus,the physiological role of caveolin-1 in cancer cells is quite complicated depending on cancer origin and other various circumstances.Investigation of expression of Caveolin-1 and its significance in renal cell carcinoma has not been reported in domestic literature.The origination and progression of neoplasm have relationships with abnormal regulation of the cell cycle.Cyclin is the most important in all of the regulation systems,among which cyclin D1 attracts most people's eyes.Cadherin is one of the big families of cell adherion molecules.In the family,E-cadherin has been a focus in researches of tumor's invasion and metastasis.Researching on expressions of Caveolin-1,cyclin D1 and E-cadherin in Renal Cell Carcinoma(RCC),evaluating the role and relationship of them in RCC could provide references to evaluation of the tumor's biological behavior and prognosis.Objective:To detect the expression of Caveolin-1,cyclin D1 and E-cadherin in different differentiated renal cell carcinorma,and analyze their associations with clinicopathological parameters.Further to compare the expression of Caveolin-1 with cyclin D1 and E-cadherin to evaluate their roles in origination and progression of RCC.To detect their mRNA expressions in different renal cell carcinoma cell lines, and guess the relationships of their expressions. Methods:(a) Expressions of Caveolin-1,cyclin D1 and E-cadherin were evaluated by immunohistochemistry in 41 renal cell carcinoma tissues in which 26 with noncancerous renal tissues.Associations between their expressions and clinical stage,tumor grade,size of tumor,and so on were analyzed.(b) Their mRNA expressions were detected quantitively by Real-time PCR in OS-RC-2 and 786-0-2.Results:(1)Among 41 tumors 17(41.5%)were considered Caveolin-1 positive. In 26 noncancerous renal tissues the positive rate was 30.8%.Significant associations between Caveolin-1 expression in RCC and clinical stage,tumor grade,and age of patient were also found(P＜0.05).(2) Positive rate of cyclin D1 expression in tumors was 46.3%.There was no one positive expression in all 26 noncancerous renal tissues, which was lower than in tumor tissues(P＜0.05).Association between cyclin D1 expression and tumor size was found(P＜0.05).The linkages between the expression of cyclin D1 and other clinicopathological parameters were not found.(3) Positive rate of E-cadherin expression in tumors was 24.4%.In noncancerous renal tissues,the rate was 50%,which was higher than in tumor tissues(P＜0.05).Association between E-cadherin expression and tumor grade was found(P＜0.05).There were no Significent associations between E-cadherin expression and other clinicopathological parameters.(4) There were no statistical relationships between the expression of Caveolin-1 and cyclin D1,so were Caveolin-1 and E-cadherin.(5) The expression of Caveolin-1 mRNA in OS-RC-2 and 786-0-2 compared with cyclin D1,E-cadherin took on 2.82,1.94 and 2408.94,13522.86 folds changing respectively.Conclusions:Caveolin-1 might have an important role in the origination and progression of renal cell carcinoma.The poorer renal cell carcinoma differentiates and the stronger it aggresses,the more caveolin-1 tumor cells secrete.The high expression of cyclin D1 and E-cadherin expression's absence may be related to the initiation of RCC.Caveolin-1 could be regarded as a candidate tumor marker for evaluation of RCC's biological behavior and prognosis of patients.