The New Molecular Targets Of Adrenal Malignant Tumor

Objective Adrenocortical carcinoma(ACC),derived from normal adrenal cortex,is a rare and highly aggressive endocrine neoplasms with very poor prognosis.At the same time,the tumor-related angiogenesis has relationship with tumor progression and tumorigenesis in a variety of tumors.As one of the most powerful inducers of angiogenesis,VEGF has a stimulate effect on the proliferation and migration of vascular endothelial cell proliferation under physiologic and pathologic conditions.And SF-1 is a nuclear receptor that demonstrated a “decisive regulator” of many aspects in the function and development of the adrenal system.Furthermore SF-1 may take part in the regulation of the angiogenesis of adrenal gland as a significant additional function.Angiopoietin 2(Ang2),belonging to angiopoietins,are secreted ligands for the tyrosine receptor kinase named Tie2.The latter one is associated with VEGF and has been deemed as a potentially significance target of SF-1 in the adrenal gland.Microvessel density(MVD) has been demonstrated as a golden standard of the evaluation of solid tumor angiogenesis.Until now the expression of SF-1,VEGF and MVD in adrenal tumors and the relationship between them have not been comprehensively understand.Therefore,we have assessed the role of the markers of angiogenesis in patients with adrenal tumors to estimate the diagnostic value of these markers in the disease of ACC,further investigate the potential targeted treatments aimed at inhibiting angiogenesis of ACC.Methods Specimens acquired from patients with human sporadic adrenocortical tumors were classified as adenomas(n=25)and carcinomas(n=27) based on the histological criteria defined by Weiss.We have assessed the immunohistochemical expression of VEGF,SF-1 and MVD in a variety of tumor samples from the aboved patients by immunohistochemistry.The staining intensity and extent were evaluated semi-quantitatively in the sample areas chosen in each block as the following standard:0-10% staining of tumor cells as 0,11-25% staining of tumor cells as 1,26-50% staining of tumor cells as 2,and staining of over 50% of tumor cells as 3. Light yellow as 1,dark yellow as 2,and brown as 3.A total score of greater than 3 was deemed positive.Results Positive staining for SF1 was seen in 74.07%(20/27) malignancy cases and 28%(7/25)benign cases showed positive staining,the difference of SF-1 expression between ACCs and ACA was statistically significant(P<0.05).And positive staining of VEGF was observed in 70.37%(19/27)of the adrenocortical carcinoma versus 32.00%(8/25)of the benign cases,the difference of VEGF expression among the two groups was statistically significant( P<0.05).The two groups had extremely significant difference(P<0.05).Furthermore,compared to ACAs group,the ACCs group was observed a higher MVD(69.22±22.56 vs 27.76±12.75,P<0.05).SF-1 was positively correlated with MVD in all specimens(r,s=0.856,P<0.0001) and the same results was observed in VEGF(r,s =0.764,P<0.0001)Conclusion The high expression of SF-1 and VEGF in adrenocortical carcinoma plays a key role in the tumor-related angiogenesis.At the same time this findings might demonstrate a promising molecular targets for the treatment of ACC.Objective To evaluate the effect of IGF1 R gene on the function of proliferation and apoptosis in human adrenocortical carcinoma cell line SW13 by tranfected Si RNA to silence the target gene.The aim of this study was to evaluate the role of Insulin-like growth factor-I receptor(IGF1R) in human adrenocortical carcinoma and seek for a new targeted therapies for ACC.Methods The expression of IGF1 R in the human adrenocortical carcinoma cell line SW13 was detected by immunofluorescence technique.According to the c DNA of human IGF1 R gene,the specific Si RNA oligos for IGF1 R was synthesized and transfected into human adrenocortical carcinoma cell line sw13 by lipofectamine 2000.After transfected for24 h,the silencing efficiency of IGF1 R m RNA was verified by realtime PCR.The expression level of IGF1 R protein was detected by western blot.And the MTT array and flow cytometry were used to demonstrate the proliferation and apoptosis of SW13 cells.Results The expression of IGF1 R was found in the human adrenocortcial carcinoma cell line SW13.The expression of IGF1 R in the level of m RNA was highly inhibited by Si RNA for IGF1 R.And the expression of this target gene in the protein level was inhibited highly too.We screened out the most efficient Si RNA-2403.The IGF1 R gene silencing may give rise to the inhibition of cell proliferation and improve the the apoptosis of SW13 cell by the means of MTT and FCM.Conclusion This experiment has demonstrated the significant role of IGF1 R in the ACC.And IGF1 R gene silencing of SW13 cells may induce apoptosis and inhibit proliferation of these cells.The inhibition of IGF1 R might be used as a new target therapies for ACC.