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Global Histone H4 Acetylation and HDAC2 Expression in Colon Adenoma and Carcinoma

  • Hassan Ashktorab
  • Kevin Belgrave
  • Fatemeh Hosseinkhah
  • Hassan Brim
  • Mehdi Nouraie
  • Mikiko Takkikto
  • Steve Hewitt
  • Edward L. Lee
  • R. H. Dashwood
  • Duane Smoot
Original Article

Abstract

Chromatin remodeling and activation of transcription are important aspects of gene regulation, but these often go awry in disease progression, including during colon cancer development. We investigated the status of global histone acetylation (by measuring H3, H4 acetylation of lysine residues, which also occur over large regions of chromatin including coding regions and non-promoter sequences) and expression of histone deacetylase 2 (HDAC2) in colorectal cancer (CRC) tissue microarrays using immunohistochemical staining. Specifically, HDAC2 and the acetylation of histones H4K12 and H3K18 were evaluated in 134 colonic adenomas, 55 moderate to well differentiated carcinomas, and 4 poorly differentiated carcinomas compared to matched normal tissue. In addition, the correlation between expression of these epigenetic biomarkers and various clinicopathological factors including, age, location, and stage of the disease were analyzed. HDAC2 nuclear expression was detected at high levels in 81.9%, 62.1%, and 53.1% of CRC, adenomas, and normal tissue, respectively (P = 0.002). The corresponding nuclear global expression levels in moderate to well differentiated tumors for H4K12 and H3K18 acetylation were increased while these levels were decreased in poorly differentiated tumors (P = 0.02). HDAC2 expression was correlated significantly with progression of adenoma to carcinoma (P = 0.002), with a discriminative power of 0.74, when comparing cancer and non-cancer cases. These results suggest HDAC2 expression is significantly associated with CRC progression.

Keywords

Global histone acetylation HDAC2 Colon cancer 

Notes

Acknowledgments

This work was supported in part by grants A102681 and CA122959 from the National Cancer Institute.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hassan Ashktorab
    • 1
    • 2
  • Kevin Belgrave
    • 1
    • 2
  • Fatemeh Hosseinkhah
    • 1
    • 2
  • Hassan Brim
    • 1
    • 3
  • Mehdi Nouraie
    • 1
    • 2
  • Mikiko Takkikto
    • 4
  • Steve Hewitt
    • 4
  • Edward L. Lee
    • 1
    • 3
  • R. H. Dashwood
    • 5
  • Duane Smoot
    • 1
    • 2
  1. 1.Department of Medicine and Cancer CenterHoward University College of MedicineWashingtonUSA
  2. 2.Howard University College of MedicineWashingtonUSA
  3. 3.Department of PathologyHoward University College of MedicineWashingtonUSA
  4. 4.Tissue Array Research Program, Laboratory of Pathology, Center for Cancer ResearchNational Cancer InstituteBethesdaUSA
  5. 5.The Linus Pauling InstituteOregon State UniversityCorvallisORUSA

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