Abstract
BackgroundTranscription factor E2F1 exerts effects on many types of cancers. As an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant transcription processes that may dominate malignancy. Clear cell renal cell carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which displays high malignancy and has a shortage of biomarkers in clinics. Our study aimed to explore the function of E2F1 in ccRCC and its correlation with clinicopathological parameters.Methodology/Principle FindingsTranscription factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The protein expression was consistent with mRNA expression. Further analysis in 92 cases indicated that E2F1 mRNA level expression was associated with the tumor pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM stage grouping and macrovascular infiltration (MAVI). These surgical specimens had high grade tumors accompanied with an elevated E2F1 expression. Moreover, E2F1 transfection was found to contribute significantly to cancer cell proliferation, migration and invasion in vitro.Conclusions/SignificanceOverexpression of E2F1 may be a key event in the local and vascular infiltration of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and MMP9. These findings highlighted the implication of E2F1’s function in the metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed to a potential new therapeutic target.
Highlights
Renal cell carcinoma (RCC) is the second leading cause of death in urological malignant neoplasms, accounting for 2% to 3% of all adult malignant diseases [1]
The expression pattern of E2F1 was evaluated by immunohistochemistry in 38 pairs of clear cell renal cell carcinoma (ccRCC) samples and corresponding noncancerous tissues
Results showed that E2F1 was mainly distributed in the cytoplasm and membrane of renal proximal tubular cells from adjacent noncancerous samples, by contrast, in ccRCC tissues nucleus was predominantly immunohistochemically stained
Summary
Renal cell carcinoma (RCC) is the second leading cause of death in urological malignant neoplasms, accounting for 2% to 3% of all adult malignant diseases [1]. The five major subtypes of RCCs are clear cell, papillary, chromophobe, collecting duct, and unclassified types. The most common subtype is clear cell renal cell carcinoma (ccRCC) [2]. The mechanism of tumor progression and vascular infiltration of ccRCC is poorly understood, and requires research on carcinogenesis and cancer development. Numerous studies have reported that E2F1 expression was of clinical significance in different cancers [6,7,8,9,10]. In vitro assay showed that E2F1 overexpression in ccRCC cell line 786-O and A498 boosted cancer cell growth and promoted the cell invasive capacity. For further investigation we explored the expression of MMP2 and MMP9, cell-surface proteolysis of extra-cellular matrix components, which may exert crucial effect in late stage carcinogenesis and vascular invasion of ccRCC
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