alpha B-Crystallin in clear cell renal cell carcinoma: Tumor progression and prognostic significance

Abstract

Objectives: AlphaB-crystallin (alpha B-crystallin), a small heat shock protein, has been reported to be involved in the growth, antiapoptosis, migration, and chemoresistance of human malignancies. Materials and methods: alpha B-crystallin expression in normal renal and clear cell renal cell carcinoma (ccRCC) tissues was examined with two-dimensional (2D) gel electrophoresis assays. Immunohistochemistry was conducted to determine the presence of alpha B-crystallin-positive tumor cells and staining intensity in 50 cases of ccRCC tissue samples. The association of alpha B-crystallin protein expression, clinicopathogic parameters and prognosis of ccRCC patients was also analyzed with Student's t-test and Kaplan-Meier analysis. Moreover, Western blot assays were performed to detect the protein expression of alpha B-crystallin in normal and tumor tissues and the alteration of cell cycle regulators in alpha B-crystallin-overexpressing cells. MTT (3[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide), BrdU, and transwell assays were performed to demonstrate the effects of aB-crystallin overexpression on cell growth, DNA synthesis and cell migration of ccRCC cells, respectively. Results: The results showed the up-regulation of alpha B-crystallin expression in ccRCC tissues. Overall survival of ccRCC patients was significantly correlated with alpha B-crystallin expression in tumor tissues. We found that aB-crystallin overexpression increased the expression of cyclin A and the incorporation of BrdU, which may be related to the enhancement of cell growth. Transwell analyses demonstrated that presence of alpha B-crystallin overexpression enhanced cell migration in ccRCC cells. Furthermore, rapamycin-resistance of tumor cells was induced when alpha B-crystallin was overexpressed. Conclusions: Our experimental findings highlight the importance of alpha B-crystallin in the tumor growth, migration, and target therapy-resistance of ccRCC cells. (C) 2013 Elsevier Inc. All rights reserved.