Expression of HDAC1 and CBP/p300 in human colorectal carcinomas

Ishihama, Katsuyoshi; Yamakawa, Mitsunori; Semba, Shuho; Takeda, Hiroaki; Kawata, Sumio; Kimura, Satoshi; Kimura, Wataru

doi:10.1136/jcp.2005.029165

Cited by 146 publications

(118 citation statements)

References 35 publications

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“…[57][58][59][60]62 Most of these studies have reported increased expression of the class I HDACs, HDAC1, 57,59,62,63 HDAC2, 57,60,62,63 HDAC3 57 and HDAC8, 57,58,60,62 in colon tumors relative to adjacent normal mucosa. Increased expression of HDACs 1, 2 and 8 in colon tumors has been demonstrated at both the protein and mRNA level, suggesting transcriptional activation may be a likely mechanism of overexpression.…”

Section: Class I and Ii Hdac Expression In Colon Cancermentioning

confidence: 99%

“…[57][58][59][60] The class I HDACs, 1, 2, 3 and 8, 52,57 and the class II HDAC, HDAC4 (Wilson and Mariadason, unpublished), are expressed in the normal colon and small intestine and primarily in the proliferating crypt compartment. The expression of HDACs 5, 6, 7, 9 and 10 in normal colon has not been reported.…”

Section: Class I and Ii Hdac Expression In Normal Colonmentioning

confidence: 99%

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HDACs and HDAC inhibitors in colon cancer

Mariadason¹

2008

Epigenetics

196

190

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Section: Class I and Ii Hdac Expression In Colon Cancermentioning

confidence: 99%

Section: Class I and Ii Hdac Expression In Normal Colonmentioning

confidence: 99%

HDACs and HDAC inhibitors in colon cancer

Mariadason¹

2008

Epigenetics

196

190

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“…Histone acetylation and deacetylation, for example, cause activation and arrest of gene transcription, respectively, and the enzymes that catalyze these changes, histone acetyltransferases (HATs) and histone deacetylases (HDACs; Kuo & Allis 1998), can also target nonhistone proteins, including transcription factors (Sterner & Berger 2000), whose dysregulated expression can have a substantial impact on cell proliferation. For these reasons, HDAC and/or HAT gene expression levels have been proposed as potential prognostic markers for several tumor types (Ishihama et al 2007, Weichert et al 2008, and histone acetylation levels have also been used (with other factors) to predict the aggressiveness of various cancers (Seligson et al 2009, Manuyakorn et al 2010, Mosashvilli et al 2010. HDACs and HATs can also be used as targets for novel anticancer drugs.…”

Section: Epigenetic Gene Regulationmentioning

confidence: 99%

Epigenetics of thyroid cancer and novel therapeutic targets

Russo¹,

Damante²,

Puxeddu³

et al. 2011

Journal of Molecular Endocrinology

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An increasing body of evidence suggests that epigenetic changes (DNA methylation, remodeling and post-translational modification of chromatin) play important roles in thyroid tumorigenesis, as a result of their effects on tumor-cell differentiation and proliferation. Epigenetic silencing of various thyroid-specific genes has been detected in thyroid tumors. These changes can diminish the tumor's ability to concentrate radioiodine, which dramatically reduces treatment options. Epigenetic changes in tumor-promoting and tumor-suppressor genes also contribute to the dysregulation of thyrocyte growth and other aspects of tumorigenesis, such as apoptosis, motility and invasiveness. We provide a brief overview of the mechanisms underlying epigenetic regulation of gene expression and the current methods used to investigate it. This is followed by a review of the principal epigenetic alterations detected in thyroid cancer cells, epigenetic strategies for treating thyroid cancers and data from preclinical and clinical studies (some still underway) on the use in this setting of demethylating agents and histone deacetylase inhibitors.

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“…HDACs can be grouped into Zn 2ϩ -dependent (class I, II, and IV) and NAD ϩ -dependent (class III) isoforms (Dokmanovic et al, 2007). Class I HDAC isoforms such as HDAC1 and HDAC3 are overexpressed in various cancers, including colon, and linked to cellular proliferation (Wilson et al, 2006;Ishihama et al, 2007;Senese et al, 2007;Spurling et al, 2008). Despite seemingly nonspecific global transcriptional effects, inhibition of Zn 2ϩ -dependent HDACs has been shown to produce significant anticancer effects in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Anticolon Cancer Activity of Largazole, a Marine-Derived Tunable Histone Deacetylase Inhibitor

Liu¹,

Salvador²,

Byeon³

et al. 2010

J Pharmacol Exp Ther

107

141

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Histone deacetylases (HDACs) are validated targets for anticancer therapy as attested by the approval of suberoylanilide hydroxamic acid (SAHA) and romidepsin (FK228) for treating cutaneous T cell lymphoma. We recently described the bioassay-guided isolation, structure determination, synthesis, and target identification of largazole, a marine-derived antiproliferative natural product that is a prodrug that releases a potent HDAC inhibitor, largazole thiol. Here, we characterize the anticancer activity of largazole by using in vitro and in vivo cancer models. Screening against the National Cancer Institute's 60 cell lines revealed that largazole is particularly active against several colon cancer cell types. Consequently, we tested largazole, along with several synthetic analogs, for HDAC inhibition in human HCT116 colon cancer cells. Enzyme inhibition strongly correlated with the growth inhibitory effects, and differential activity of largazole analogs was rationalized by molecular docking to an HDAC1 homology model. Comparative genomewide transcript profiling revealed a close overlap of genes that are regulated by largazole, FK228, and SAHA. Several of these genes can be related to largazole's ability to induce cell cycle arrest and apoptosis. Stability studies suggested reasonable bioavailability of the active species, largazole thiol. We established that largazole inhibits HDACs in tumor tissue in vivo by using a human HCT116 xenograft mouse model. Largazole strongly stimulated histone hyperacetylation in the tumor, showed efficacy in inhibiting tumor growth, and induced apoptosis in the tumor. This effect probably is mediated by the modulation of levels of cell cycle regulators, antagonism of the AKT pathway through insulin receptor substrate 1 down-regulation, and reduction of epidermal growth factor receptor levels.

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Expression of HDAC1 and CBP/p300 in human colorectal carcinomas

Abstract: Results showed the up-regulation of these three histone-modifying molecules in this series of colorectal cancers and suggested that monitoring of CBP and p300 may assist prediction of the prognosis in patients with colorectal adenocarcinoma.

Cited by 146 publications

References 35 publications

HDACs and HDAC inhibitors in colon cancer

HDACs and HDAC inhibitors in colon cancer

Epigenetics of thyroid cancer and novel therapeutic targets

Anticolon Cancer Activity of Largazole, a Marine-Derived Tunable Histone Deacetylase Inhibitor

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