Identification of genes up-regulated by histone deacetylase inhibition with cDNA microarray and exploration of epigenetic alterations on hepatoma cells

Chiba, Tetsuhiro; Yokosuka, Osamu; Arai, Makoto; Tada, Motohisa; Fukai, Kenichi; Imazeki, Fumio; Kato, Masaki; Seki, Naohiko; Saisho, Hiromitsu

doi:10.1016/j.jhep.2004.05.018

Cited by 92 publications

(73 citation statements)

References 41 publications

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“…In a search for transcriptional targets critical for HDAC inhibitor-induced anti-cancer effects, we reviewed published cDNA microarray gene profiling studies and found that TG2 is commonly up-regulated by HDAC inhibitors, such as Trichostatin A (TSA), SAHA, and butyrate, in cancer cells of various organ origins, such as leukaemia and liver, renal, nasopharyngeal, and breast cancer (13)(14)(15)(16). To validate this observation, we performed semiquantitative RT-PCR analysis of TG2 gene expression in neuroblastoma and breast cancer cells.…”

Section: Resultsmentioning

confidence: 99%

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Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis

Liu

Tee

Porro

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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Histone deacetylase (HDAC) inhibitors reactivate tumor suppressor gene transcription; induce cancer cell differentiation, growth arrest, and programmed cell death; and are among the most promising new classes of anticancer drugs. Myc oncoproteins can block cell differentiation and promote cell proliferation and malignant transformation, in some cases by modulating target gene transcription. Here, we show that tissue transglutaminase (TG2) was commonly reactivated by HDAC inhibitors in neuroblastoma and breast cancer cells but not normal cells and contributed to HDAC inhibitor-induced growth arrest. TG2 was the gene most significantly repressed by N-Myc in neuroblastoma cells in a cDNA microarray analysis and was commonly repressed by N-Myc in neuroblastoma cells and c-Myc in breast cancer cells. Repression of TG2 expression by N-Myc in neuroblastoma cells was necessary for the inhibitory effect of N-Myc on neuroblastoma cell differentiation. Dual step cross-linking chromatin immunoprecipitation and protein coimmunoprecipitation assays showed that N-Myc acted as a transrepressor by recruiting the HDAC1 protein to an Sp1-binding site in the TG2 core promoter in a manner distinct from it's action as a transactivator at E-Box binding sites. HDAC inhibitor treatment blocked the N-Myc-mediated HDAC1 recruitment and TG2 repression in vitro . In neuroblastoma-bearing N-Myc transgenic mice, HDAC inhibitor treatment induced TG2 expression and demonstrated marked antitumor activity in vivo . Taken together, our data indicate the critical roles of HDAC1 and TG2 in Myc-induced oncogenesis and have significant implications for the use of HDAC inhibitor therapy in Myc-driven oncogenesis.

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Section: Resultsmentioning

confidence: 99%

“…We found that published cDNA microarray gene profiling studies of HDAC inhibitor-treated cell lines and tissues identified tissue transglutaminase (TG2) as one of the common transcriptional targets of HDAC inhibitors (13)(14)(15)(16). Our own microarray data showed that TG2 was the gene most significantly repressed by N-Myc in neuroblastoma cells.…”

mentioning

confidence: 89%

Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis

Liu

Tee

Porro

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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“…In our previous report, we showed that Sp-1 induces GST-M2 expression in lung cells but is destroyed by a DNA-hypermethylated epigenetic mechanism (10). Recent studies have proposed that histone deacetylase inhibitors, trichostatin (TSA), and mediated CCN2 regulation are conferred by a short proximal promoter construct that contains 2 Sp-1 sites (44)(45)(46). Here, we showed that low expression of GST-M2 with CCN2 leads to poor overall survival (Table 1).…”

Section: Discussionmentioning

confidence: 67%

Glutathione S-Transferase Mu2 Suppresses Cancer Cell Metastasis in Non–Small Cell Lung Cancer

Tang

Lai

et al. 2013

Molecular Cancer Research

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Glutathione S-transferase mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers is due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2-defective cells in lung cancer, has not been established. In the present study, we investigate the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. GST-M2 and CCN2 mRNA levels were significantly reduced in non-small cell lung cancer (NSCLC) tumors when compared with matched normal lung tissues in 82 patients with NSCLC. We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression. GST-M2 can induce CCN2 expression by driving the CCN2 proximal promoter. Overexpression of GST-M2 decreases the formation of filopodia, resulting in remodeling of the reorganized cytoskeletons. Overexpression of GST-M2 significantly suppressed cancer cell migration on wound-healing assay. In addition, overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mouse model. These data highlight the potential of GST-M2 as a novel tumor suppressor. GST-M2 increases the expression of CCN2 in lung cancer cells, which inhibits cancer cell migration in lung cancer and animal models. Mol Cancer Res; 11(5); 518-29. Ó2013 AACR.

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“…4 Histone deacetylase (HDAC) inhibitors have been the focus of many recent preclinical and clinical investigations because of their ability to induce growth arrest, differentiation, and apoptosis in multiple types of human cancer cells, [13][14][15] including those of the liver. [16][17][18][19][20][21][22][23][24] The accepted model for the anticancer mechanism of HDAC inhibitors has been drug-induced hyperacetylation of core histones leading to chromatin remodeling and reactivated expression of genes regulating cell proliferation, cell cycle progression, and cell survival. 13,14,[25][26][27][28] In addition to this histone acetylation-dependent modulation of transcription, histone acetylation-independent mechanisms involving a number of nonhistone HDAC substrates have been implicated in the anticancer activities of HDAC inhibitors, 15,29,30 many of which participate in important signaling pathways such as nuclear factor B, signal transducer and activator of transcription 3, p53, and heat shock protein-90.…”

mentioning

confidence: 99%

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

Kashida

Kulp

et al. 2007

Hepatology

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H epatocellular carcinoma (HCC) is the fifth most common human cancer and third most frequent cause of cancer death worldwide. 1 Although over 80% of new HCC cases will occur in Eastern Asia and subSaharan Africa, 2 the startling increase in HCC incidence in the United States over the past 20-25 years and the typically high mortality from this disease have established HCC as an important health concern in this country. [2][3][4][5][6] The clinical management of HCC is complicated by typically late-stage disease at presentation and prevalent underlying liver dysfunction that can render patients ineligible for potentially curative surgical therapies, which are generally suitable for only 20%-30% of HCC patients. 3,5,7 Although regional therapies, such as transarterial embolization and percutaneous treatments, are used in patients with nonresectable disease, their success is curtailed by recurrence as locally advanced or metastatic disease. For these patients, systemic therapy is indicated but has been largely unsuccessful. 3,4,[8][9][10] Thus, a clear need exists to develop effective, life-prolonging therapeutic strategies for the large number of HCC patients with advanced disease.A major challenge in the systemic treatment of HCC is cellular resistance to conventional cytotoxic agents, which, at

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Identification of genes up-regulated by histone deacetylase inhibition with cDNA microarray and exploration of epigenetic alterations on hepatoma cells

Cited by 92 publications

References 41 publications

Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis

Activation of tissue transglutaminase transcription by histone deacetylase inhibition as a therapeutic approach for Myc oncogenesis

Glutathione S-Transferase Mu2 Suppresses Cancer Cell Metastasis in Non–Small Cell Lung Cancer

Efficacy of a novel histone deacetylase inhibitor in murine models of hepatocellular carcinoma

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