Association of changes in expression of and genes after drug treatment with cancer cell line sensitivity to kinase inhibitors

Authors

Julia Krushkal, Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
Yingdong Zhao, Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
Kyle Roney, Department of Biostatistics and Bioinformatics, George Washington University, Washington, DC, USA.
Weimin Zhu, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Alan Brooks, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Deborah Wilsker, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Ralph E. Parchment, Clinical Pharmacodynamic Biomarkers Program, Applied/Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Lisa M. McShane, Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
James H. Doroshow, Division of Cancer Treatment and Diagnosis and Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Document Type

Journal Article

Publication Date

12-1-2024

Journal

Epigenetics

Volume

19

Issue

1

DOI

10.1080/15592294.2024.2309824

Keywords

HDAC5; Histone deacetylase; chemosensitivity; dasatinib; sirtuin

Abstract

Histone deacetylases (HDACs) and sirtuins (SIRTs) are important epigenetic regulators of cancer pathways. There is a limited understanding of how transcriptional regulation of their genes is affected by chemotherapeutic agents, and how such transcriptional changes affect tumour sensitivity to drug treatment. We investigated the concerted transcriptional response of and genes to 15 approved antitumor agents in the NCI-60 cancer cell line panel. Antitumor agents with diverse mechanisms of action induced upregulation or downregulation of multiple and genes. was upregulated by dasatinib and erlotinib in the majority of the cell lines. Tumour cell line sensitivity to kinase inhibitors was associated with upregulation of , and several genes. We confirmed changes in and expression in independent datasets. We also experimentally validated the upregulation of HDAC5 mRNA and protein expression by dasatinib in the highly sensitive IGROV1 cell line. HDAC5 was not upregulated in the UACC-257 cell line resistant to dasatinib. The effects of cancer drug treatment on expression of and genes may influence chemosensitivity and may need to be considered during chemotherapy.

APA Citation

Krushkal, Julia; Zhao, Yingdong; Roney, Kyle; Zhu, Weimin; Brooks, Alan; Wilsker, Deborah; Parchment, Ralph E.; McShane, Lisa M.; and Doroshow, James H., "Association of changes in expression of and genes after drug treatment with cancer cell line sensitivity to kinase inhibitors" (2024). GW Authored Works. Paper 4264.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4264

Department

Biostatistics and Bioinformatics