Screening for therapeutic targets of vorinostat by SILAC-based proteomic analysis in human breast cancer cells

Qun Zhou, Raghothama Chaerkady, Patrick G. Shaw, Thomas W. Kensler, Akhilesh Pandey, Nancy E. Davidson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Histone deacetylases (HDACs) play critical roles in silencing tumor suppressor genes. HDAC inhibitors reactivate tumor suppressor genes and inhibit tumor cell growth in vitro and in vivo, and several HDAC inhibitors are currently being evaluated in clinical trials for cancer therapy. A comprehensive analysis of proteins regulated by HDAC inhibitors would enhance our ability to define and characterize their essential therapeutic targets. Here, we employed stable isotope labeling with amino acids in cell culture-based quantitative proteomics to identify acetylated proteins in human breast cancer cells. Treatment with the clinically relevant HDAC inhibitor, suberoylanilide hydroxamic acid (vorinostat), induces lysine acetylation of 61 proteins in MDA-MB-231 human breast cancer cells. Suberoylanilide hydroxamic acid not only induces lysine acetylation in chromatin-associated proteins, but also acetylates previously unrecognized nonhistone proteins, including transcriptional factors and regulators, chaperones, cell structure proteins, and glycolytic enzymes in a time-dependent manner. Knowledge of the full repertoire of acetylated proteins will provide a foundation for further defining the functions of HDACs in cancer cells. & 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

Original languageEnglish (US)
Pages (from-to)1029-1039
Number of pages11
JournalProteomics
Volume10
Issue number5
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Histone Deacetylases
Proteomics
Screening
Cells
Breast Neoplasms
Proteins
Tumors
Acetylation
Tumor Suppressor Genes
Therapeutics
Lysine
Genes
Isotope Labeling
Neoplasms
Cell growth
vorinostat
Cell culture
Isotopes
Labeling
Chromatin

Keywords

  • Biomedicine
  • Breast cancer
  • Protein profile
  • Quantitative analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry

Cite this

Screening for therapeutic targets of vorinostat by SILAC-based proteomic analysis in human breast cancer cells. / Zhou, Qun; Chaerkady, Raghothama; Shaw, Patrick G.; Kensler, Thomas W.; Pandey, Akhilesh; Davidson, Nancy E.

In: Proteomics, Vol. 10, No. 5, 01.03.2010, p. 1029-1039.

Research output: Contribution to journalArticle

Zhou, Qun ; Chaerkady, Raghothama ; Shaw, Patrick G. ; Kensler, Thomas W. ; Pandey, Akhilesh ; Davidson, Nancy E. / Screening for therapeutic targets of vorinostat by SILAC-based proteomic analysis in human breast cancer cells. In: Proteomics. 2010 ; Vol. 10, No. 5. pp. 1029-1039.
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