Abstract

Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and-9 as being associated with basal–squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4,-7, and-9 in basal BC cell lines (p < 0.05; Kruskal–Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4,-7, and-9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.

Original languageEnglish (US)
Article number2599
JournalInternational journal of molecular sciences
Volume20
Issue number10
DOIs
StatePublished - May 2 2019

Fingerprint

Histone Deacetylases
bladder
Polymerase chain reaction
Urinary Bladder Neoplasms
cancer
Cells
Genes
polymerase chain reaction
Aberrations
Muscle
Tumors
Real-Time Polymerase Chain Reaction
cultured cells
Enzymes
Atlases
Cell Line
genome
Genome
In Vitro Techniques
Neoplasms

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

@article{24d4462955df417ab46e2a0c24b76fbd,
title = "Characterization of histone deacetylase expression within in vitro and in vivo bladder cancer model systems",
abstract = "Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and-9 as being associated with basal–squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4,-7, and-9 in basal BC cell lines (p < 0.05; Kruskal–Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4,-7, and-9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.",
author = "Buckwalter, {Jenna M.} and Wilson Chan and Lauren Shuman and Thomas Wildermuth and Justine Ellis-Mohl and Vonn Walter and Warrick, {Joshua I.} and Wu, {Xue Ru} and Matt Kaag and Raman, {Jay D.} and Degraff, {David J.}",
year = "2019",
month = "5",
day = "2",
doi = "10.3390/ijms20102599",
language = "English (US)",
volume = "20",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
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Characterization of histone deacetylase expression within in vitro and in vivo bladder cancer model systems. / Buckwalter, Jenna M.; Chan, Wilson; Shuman, Lauren; Wildermuth, Thomas; Ellis-Mohl, Justine; Walter, Vonn; Warrick, Joshua I.; Wu, Xue Ru; Kaag, Matt; Raman, Jay D.; Degraff, David J.

In: International journal of molecular sciences, Vol. 20, No. 10, 2599, 02.05.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Characterization of histone deacetylase expression within in vitro and in vivo bladder cancer model systems

AU - Buckwalter, Jenna M.

AU - Chan, Wilson

AU - Shuman, Lauren

AU - Wildermuth, Thomas

AU - Ellis-Mohl, Justine

AU - Walter, Vonn

AU - Warrick, Joshua I.

AU - Wu, Xue Ru

AU - Kaag, Matt

AU - Raman, Jay D.

AU - Degraff, David J.

PY - 2019/5/2

Y1 - 2019/5/2

N2 - Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and-9 as being associated with basal–squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4,-7, and-9 in basal BC cell lines (p < 0.05; Kruskal–Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4,-7, and-9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.

AB - Epigenetic aberrations are prominent in bladder cancer (BC) and contribute to disease pathogenesis. We characterized histone deacetylase (HDAC) expression, a family of deacetylation enzymes, in both in vitro and in vivo BC model systems and analyzed expression data from The Cancer Genome Atlas (TCGA). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis was used to determine the expression status of Class I and II HDACs in ten human BC cell lines, while qRT-PCR was used to determine HDAC expression in 24 human tumor specimens. The TCGA cohort consists of 408 muscle invasive BC (MIBC) clinical samples and analysis of this data set identified expression of HDAC4 and-9 as being associated with basal–squamous disease. These findings agree with qRT-PCR results identifying increased expression of HDAC4,-7, and-9 in basal BC cell lines (p < 0.05; Kruskal–Wallis test) and in clinical specimens with invasive bladder cancer (not statistically significant). We also observed increased expression in Hdac4,-7, and-9 in commonly used BC mouse models. Here, we identify suitable preclinical model systems for the study of HDACs, and show increased expression of Class IIa HDACs, specifically HDAC4 and HDAC9, in basal BC cell lines and in invasive clinical specimens. These results suggest this class of HDACs may be best suited for targeted inhibition in patients with basal BC.

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