Antibody response to a non‐conserved C‐terminal part of human histone deacetylase 3 in colon cancer patients

Shebzukhov, Yuriy V.; Koroleva, Ekaterina P.; Khlgatian, Svetlana V.; Belousov, Pavel V.; Kuz'mina, Ksenia E.; Radko, Boris V.; Longpré, Fanny; Lagarkova, Maria A.; Kadachigova, Tatiana S.; Гурова, О В; Meshcheryakov, Andrey; Lichinitser, Mikhail; Jäger, Elke; Kuprash, Dmitry V.; Nedospasov, Sergei A.

doi:10.1002/ijc.21240

Cited by 20 publications

(12 citation statements)

References 28 publications

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“…HDAC2 expression is increased in human colon cancer, in which there is a loss of APC tumor suppressor (19). HDAC3 expression is increased in human tumor samples of colon cancer compared with normal tissue (18,20). HDAC5 is downregulated in colon cancer (21).…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors selectively suppress expression of HDAC7

Dokmanovic

Pérez²,

Xu³

et al. 2007

Molecular Cancer Therapeutics

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There are 18 histone deacetylases (HDAC) generally divided into four classes based on homology to yeast HDACs. HDACs have many protein substrates in addition to histones that are involved in regulation of gene expression, cell proliferation, and cell death. Inhibition of HDACs can cause accumulation of acetylated forms of these proteins, thus altering their function. HDAC inhibitors (HDACi), such as the hydroxamic acid -based vorinostat (suberoylanilide hydroxamic acid), inhibit the zinc-containing classes I, II, and IV, but not the NAD + -dependent class III, enzymes. HDACis are a group of novel anticancer agents. Vorinostat is the first HDACi approved for clinical use in the treatment of the cancer cutaneous T-cell lymphoma. Factors affecting expression of HDACs are not well understood. This study focuses on the effect of the HDACi vorinostat on the expression of class I and class II HDACs. We found that vorinostat selectively down-regulates HDAC7 with little or no effect on the expression of other class I or class II HDACs. Fourteen cell lines were examined, including normal, immortalized, genetically transformed, and human cancer-derived cell lines. Down-regulation of HDAC7 by vorinostat is more pronounced in transformed cells sensitive to inhibitorinduced cell death than in normal cells or cancer cells resistant to induced cell death. Modulation of HDAC7 levels by small interfering RNA -mediated knockdown or by HDAC7 overexpression is associated with growth arrest but without detectable changes in acetylation of histones or p21 gene expression. Selective down-regulation of HDAC7 protein may serve as a marker of response of tumors to HDACi. [Mol Cancer Ther 2007;6(9):2525 -34]

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Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors selectively suppress expression of HDAC7

Dokmanovic

Pérez²,

Xu³

et al. 2007

Molecular Cancer Therapeutics

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“…This finding provides an interesting possible functional explanation for the long known interlink between nutrition and colorectal cancer formation. Finally, the detection of antibodies directed against HDAC3 has been suggested as a serologic antigen/biomarker for colorectal cancer (15).…”

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confidence: 99%

Class I Histone Deacetylase Expression Has Independent Prognostic Impact in Human Colorectal Cancer: Specific Role of Class I Histone Deacetylases In vitro and In vivo

Weichert

Roske

Niesporek

et al. 2008

Clinical Cancer Research

332

217

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Purpose: Recently, several studies reported a strong functional link betweenhistone deacetylases (HDAC) and the development of tumors of the large intestine. However, despite the importance of these molecules, comparably little is known on expressionpatterns and functions of specific HDAC isoforms in colorectal cancer. Experimental Design: We characterized class I HDAC isoform expression patterns in a cohort of 140 colorectal carcinomas by immunohistochemistry. In addition, effects of HDAC inhibition by valproic acid and suberoylanilide hydroxamic acid, and specific HDAC isoform knockdown by short interfering RNA, were investigated in a cell culture model. Results: We found class I HDACs highly expressed in a subset of colorectal carcinomas with positivity for HDAC1 in 36.4%, HDAC2 in 57.9%, and HDAC3 in 72.9% of cases. Expression was significantly enhanced in strongly proliferating (P = 0.002), dedifferentiated (P = 0.022) tumors. High HDAC expression levels implicated significantly reduced patient survival (P = 0.001), with HDAC2 expression being an independent survival prognosticator (hazard ratio, 2.6; P = 0.03). Short interfering RNA^based inhibition of HDAC1 and HDAC2 but not HDAC3 suppressed growth of colon cancer cells in vitro, although to a lesser extent than chemical HDAC inhibitors did. Conclusions: The strong prognostic impact of HDAC isoforms in colorectal cancer, the interactions of HDACs with tumor cell proliferation and differentiation in vivo, and our finding that HDACs are differentially expressed in colorectal tumors suggest that the evaluation of HDAC expression in clinical trials for HDAC inhibitors might help to identify a patient subgroup who will exceptionally profit from such a treatment.

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“…Of the 5 SEREX-based antigens examined in this study, serum samples from colorectal cancer patients reacted to rCCCAP with the highest frequency (35.1%) and to rNY-CO-16 with the lowest frequency (18.1%). Similarly, Scanlan et al 34 demonstrated a frequency of serological response to 13 colorectal cancer-related antigens of 3-8% and Shebzukhov et al 37 identified HDAC3 as a novel serological antigen for colon cancer detection with a 5% serological response frequency. A compilation of anti-p53 studies indicates the reaction frequency among colorectal cancer patient serum samples was 15-24.6%.…”

Section: Discussionmentioning

confidence: 97%

Multiple serological biomarkers for colorectal cancer detection

Chan

Fan

Kuo

et al. 2010

Intl Journal of Cancer

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The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumorassociated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (!5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients.

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Antibody response to a non‐conserved C‐terminal part of human histone deacetylase 3 in colon cancer patients

Cited by 20 publications

References 28 publications

Histone deacetylase inhibitors selectively suppress expression of HDAC7

Histone deacetylase inhibitors selectively suppress expression of HDAC7

Class I Histone Deacetylase Expression Has Independent Prognostic Impact in Human Colorectal Cancer: Specific Role of Class I Histone Deacetylases In vitro and In vivo

Multiple serological biomarkers for colorectal cancer detection

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