TY - JOUR
T1 - Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma
AU - Ashktorab, Hassan
AU - Belgrave, Kevin
AU - Hosseinkhah, Fatemeh
AU - Brim, Hassan
AU - Nouraie, Mehdi
AU - Takkikto, Mikiko
AU - Hewitt, Steve
AU - Lee, Edward L.
AU - Dashwood, R. H.
AU - Smoot, Duane
N1 - Funding Information:
Acknowledgments This work was supported in part by grants A102681 and CA122959 from the National Cancer Institute.
PY - 2009/10
Y1 - 2009/10
N2 - 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.
AB - 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.
KW - Colon cancer
KW - Global histone acetylation
KW - HDAC2
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U2 - 10.1007/s10620-008-0601-7
DO - 10.1007/s10620-008-0601-7
M3 - Article
C2 - 19057998
AN - SCOPUS:70149103990
SN - 0163-2116
VL - 54
SP - 2109
EP - 2117
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 10
ER -