期刊
JOURNAL OF UROLOGY
卷 180, 期 3, 页码 1131-1136出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.juro.2008.04.136
关键词
kidney; carcinoma, renal cell; acetylation; histones; gene expression
Purpose: Recent studies suggest that alterations in chromatin structure by histone acetylation may have an important role in the neoplastic process. We evaluated histone H3, acetylation in renal cell carcinoma and the effects of a histone deacetylase inhibitor on renal cancer cell lines. Materials and Methods: The expression of acetylated histone H3 (Lys9) in renal cell carcinoma and corresponding nonneoplastic tissue specimens was evaluated. We next assessed immunohistologically the relationships between acetylated histone H3 expression and clinicopathological. parameters in 44 cases of renal cell carcinoma. Furthermore, we evaluated the effects of the histone deacetylase inhibitor depsipeptide on the renal cancer cell lines Caki-1, ACHN, 769P and 7860 (ATCC (R)). Results: Acetylated histone H3 expression was decreased in 85.0% of renal cell carcinomas compared to levels in nonneoplastic tissue: Decreased expression was related to high nuclear tumor grade and advanced pathological tumor stage (p = 0.048 and 0.032, respectively). Depsipeptide inhibited cell line proliferation in a time and dose dependent manner. Depsipeptide induced apoptosis in Caki-1, ACHN and 7860, and induced G2 cell cycle arrest in 769P. Concomitantly depsipeptide increased acetylated histone H3 and p21(WAF/CIP1) expression, and induced Bcl-2 phosphorylation. Conclusions: These results suggest that the decreased acetylation of histone H3 is a common alteration in a malignant phenotype of renal cell carcinoma. Increasing the amount of acetylated histone H3 might be a therapeutic option for renal cell carcinoma.
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