Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression

Junko Suzuki, Yunn Yi Chen, Gary K. Scott, Sandy DeVries, Kwang-Yung Chin, Christopher C. Benz, Frederic M. Waldman, E. Shelley Hwang

Research output: Contribution to journalArticle

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Abstract

Purpose: Excess histone deacetylase (HDAC) activity can induce hypoacetylation of histone and nonhistone protein substrates, altering gene expression patterns and cell behavior potentially associated with malignant transformation. However, HDAC expression and protein acetylation have not been studied in the context of breast cancer progression. Experimental Design: We assessed expression levels of acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in 22 reduction mammoplasties and in 58 specimens with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Differences among groups were tested for significance using nonparametric tests. Results: From normal epithelium to DCIS, there was a marked reduction in histone acetylation (P <0.0001). Most cases showed similar levels of acetylation in DCIS and IDC, although some showed further reduction of ac-H4 and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also significantly reduced but by a smaller magnitude. Greater reductions of H4 acetylation and HDAC1 levels were observed from normal to DCIS in estrogen receptor-negative compared with estrogen receptor-positive, and in high-grade compared with non-high-grade tumors. Conclusion: Overall, there was a global pattern of hypoacetylation associated with progression from normal to DCIS to IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and IDC could be an early measure of HDAC inhibitor activity.

Original languageEnglish (US)
Pages (from-to)3163-3171
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number9
DOIs
StatePublished - May 1 2009
Externally publishedYes

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Carcinoma, Intraductal, Noninfiltrating
Histone Deacetylases
Acetylation
Ductal Carcinoma
Breast Neoplasms
Histones
Proteins
Estrogen Receptors
Epithelium
Histone Deacetylase Inhibitors
Mammaplasty
Tubulin
Research Design
Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression. / Suzuki, Junko; Chen, Yunn Yi; Scott, Gary K.; DeVries, Sandy; Chin, Kwang-Yung; Benz, Christopher C.; Waldman, Frederic M.; Hwang, E. Shelley.

In: Clinical Cancer Research, Vol. 15, No. 9, 01.05.2009, p. 3163-3171.

Research output: Contribution to journalArticle

Suzuki, Junko ; Chen, Yunn Yi ; Scott, Gary K. ; DeVries, Sandy ; Chin, Kwang-Yung ; Benz, Christopher C. ; Waldman, Frederic M. ; Hwang, E. Shelley. / Protein acetylation and histone deacetylase expression associated with malignant breast cancer progression. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 9. pp. 3163-3171.
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