Alterations of the gene expression profile in renal cell carcinoma after treatment with the histone deacetylase-inhibitor valproic acid and interferon-alpha.

World Journal of Urology
Eva JuengelRoman A Blaheta

Abstract

Renal cell carcinoma (RCC) is highly resistant to chemotherapy and unresponsive to radio- and immunotherapy. Recently, we have documented that the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) in combination with low-dosed interferon (IFN)-alpha significantly inhibits RCC proliferation and adhesion in vitro and in vivo. The current study investigated the effects of these compounds on gene transcription of metastatic RCC cell line Caki-1 after 3 and 5 days exposure. To evaluate the gene expression profiles of the RCC cells, we performed microarray analysis using Affymetrix GeneChip. Selected significant genes were further validated by Real Time PCR. Microarray revealed that VPA altered genes that are involved in cell growth, cell survival, immune response, cell motility and cell adhesion. Combination of VPA with IFN-alpha not only enhanced the effects on gene transcription but also resulted in the expression of novel genes, which were not induced by either VPA or IFN-alpha alone. Among the up-regulated genes were chemokines (CXCL10, CXCL11, CXCL16) and integrins (ITGA2, ITGA4, ITGA5, ITGA6, ITGA7). Genes encoding for adhesion molecules (NCAM1, ICAM1, VCAM1) were also modulated. Real Time PCR approved these findings. T...Continue Reading

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Citations

May 2, 2014·Journal of Cellular and Molecular Medicine·Jasmina MakarevićRoman A Blaheta
Aug 21, 2015·Journal of Thyroid Research·Shailendra Kapoor
Jul 9, 2013·The American Journal of Pathology·Lang-Zhu TanJian-Hua Luo
Feb 6, 2020·International Journal of Molecular Sciences·João LoboRui Henrique
Nov 9, 2011·Immunology and Cell Biology·Graham R Leggatt, Brian Gabrielli
Mar 8, 2019·International Journal of Molecular Sciences·Himavanth Reddy GatlaMonish Ram Makena
Nov 19, 2020·International Journal of Molecular Sciences·Monika Gudowska-SawczukBarbara Mroczko

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