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

Pei Yin Ho, Shih Chieh Chueh, Shyh Horng Chiou, Shuo Meng Wang, Wei Chou Lin, I. Liang Lee, Hsin Yi Yang, Hsiang Chi Peng, Ming Kuen Lai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

19 Scopus citations

Abstract

Objectives: AlphaB-crystallin (αB-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: αB-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 αB-crystallin-positive tumor cells and staining intensity in 50 cases of ccRCC tissue samples. The association of αB-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 αB-crystallin in normal and tumor tissues and the alteration of cell cycle regulators in αB-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 αB-crystallin overexpression on cell growth, DNA synthesis and cell migration of ccRCC cells, respectively. Results: The results showed the up-regulation of αB-crystallin expression in ccRCC tissues. Overall survival of ccRCC patients was significantly correlated with αB-crystallin expression in tumor tissues. We found that αB-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 αB-crystallin overexpression enhanced cell migration in ccRCC cells. Furthermore, rapamycin-resistance of tumor cells was induced when αB-crystallin was overexpressed. Conclusions: Our experimental findings highlight the importance of αB-crystallin in the tumor growth, migration, and target therapy-resistance of ccRCC cells.

Original languageEnglish
Pages (from-to)1367-1377
Number of pages11
JournalUrologic Oncology: Seminars and Original Investigations
Volume31
Issue number7
DOIs
StatePublished - 10 2013
Externally publishedYes

Keywords

  • Clear cell renal cell carcinoma
  • Drug resistance
  • Migration
  • Prognostic factor
  • Proliferation
  • αB-crystallin

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