Role of Epigenetics in Testicular Cancer Cell Drug Response

Yerby, Clifford J

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https://hdl.handle.net/2142/109946 Copy

Description

Title

Role of Epigenetics in Testicular Cancer Cell Drug Response

Author(s)

Yerby, Clifford J

Issue Date

2021

Department of Study

Comparative Biosciences

Discipline

Biochemistry

Degree Granting Institution

University of Illinois at Urbana

Degree Name

B.S. (bachelor's)

Degree Level

Thesis

Keyword(s)

• Testicular Germ Cell Tumors (TGCTs)
• Cisplatin
• Chemotherapeutic Resistance

Language

en

Abstract

Testicular cancer is highly curable with the chemotherapeutic cisplatin. However, 15-20% of patients are resistant and succumb to their disease. Previously we showed that cisplatin refractory testicular cancer is highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). The mechanisms for cisplatin sensitivity and resistance in testicular cancer is unclear. If we can understand why testicular cancer is so curable, this knowledge could be applied to other cancer types. To better understand the mechanism of chemotherapy sensitivity and resistance in testicular cancer cells our lab generated two series of cell models, one resistant to cisplatin and the other resistant to 5- aza. We noted a reciprocal relationship between cisplatin and 5-aza resistance, with cisplatin resistance associated with increased sensitivity to 5-aza and 5-aza resistance associated with increased sensitivity to cisplatin. Transcriptomics revealed downregulation of the H3K27me3-mediated polycomb pathway in cisplatin resistant cells and upregulation of this pathway with 5-Aza resistance. To explore possible mechanisms for this reciprocal epigenetic modeling, the expression of the gene family responsible for histone lysine demethylation, the KDM family, was assessed by qPCR. Many KDM genes, including those responsible for H3K27me3 demethylation, were upregulated in cisplatin resistant cells and downregulated in 5-Aza resistant cells. Changes in KDM gene expression could explain, in part, globally altered levels of H3K27 methylation. We are performing genetic and pharmacologic studies to further validate a role for the H3K27me3 polycomb pathway in chemotherapeutic resistance, with the goal of devising novel therapies for testicular and potentially other cancers.

Type of Resource

text

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http://hdl.handle.net/2142/109946

Copyright and License Information

Copyright 2020 Clifford Yerby

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