Differential effects of histone deacetylase inhibitors on phorbol ester‐ and TGF‐β1 induced murine <i>tissue inhibitor of metalloproteinases‐1</i> gene expression

Young, David A.; Billingham, Olivia; Sampieri, Clara Luz; Edwards, Dylan R.; Clark, Ian M.

doi:10.1111/j.1742-4658.2005.04622.x

Cited by 27 publications

(36 citation statements)

References 48 publications

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“…1). Previously, we reported that the HDAC inhibitor TSA could prevent the induction of Timp-1 by TGF-β in murine C3H10T1/2 and swiss-3T3 fibroblasts, implicating a role for HDACs in Timp-1 expression (Young et al, 2005). We confirmed this result and tested whether Adam12 and Pai-1 were also repressed by TSA (Fig.…”

Section: Histone Deacetylases Regulate a Subset Of Tgf-β-induced Genessupporting

confidence: 76%

“…We have previously demonstrated that the induction of Timp-1 expression by TGF-β is dependent on the intermediate expression of immediate early response genes such as the AP-1 transcription factors (Young et al, 2005). We have also found that the expression of a number of TGF-β-induced AP-1 proteins is repressed by TSA (Young et al, 2005 and Supp.…”

Section: Hdac3 Regulates the Tgf-β Induction Of Activator Proteinssupporting

confidence: 49%

“…We have also found that the expression of a number of TGF-β-induced AP-1 proteins is repressed by TSA (Young et al, 2005 and Supp. Fig.…”

Section: Hdac3 Regulates the Tgf-β Induction Of Activator Proteinsmentioning

confidence: 75%

“…We used real-time RT-PCR to measure the time-course of Adam12, Timp-1 and Pai-1 induction by TGF-β in the murine pluripotent mesenchymal C3H10T1/2 cell line, which has been widely used to study responses to the TGF-β family of growth factors (Denker et al, 1995;Wang et al, 1993;Young et al, 2005). Adam12 and Timp-1 induction was a late event, maximal at 8 h (Fig.…”

Section: Histone Deacetylases Regulate a Subset Of Tgf-β-induced Genesmentioning

confidence: 99%

“…In addition, global HDAC inhibition with trichostatin A (TSA), a non-selective general HDAC inhibitor, causes the repression of a subset of TGF-β-induced genes (Ghosh et al, 2007;Glenisson et al, 2007;Kuang et al, 2007;Rombouts et al, 2002) and suppresses TGF-β-induced epithelial-tomesenchymal transition in human renal epithelial cells (Yoshikawa et al, 2007). We previously reported that HDAC inhibitors also repressed TGF-β-induced Timp-1 expression (Young et al, 2005), providing insight into the mechanisms underlying Timp-1 expression and offering the opportunity of modulating Timp-1 expression in pathology. However, the mechanisms of HDAC inhibitor-mediated repression of TGF-β-induced gene expression remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Barter¹,

Pybus²,

Litherland³

et al. 2010

Matrix Biology

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a b s t r a c t a r t i c l e i n f oHistone deacetylases (HDACs) regulate the acetylation of histones in the control of gene expression. Many non-histone proteins are also targeted for acetylation, including TGF-β signalling pathway components such as Smad2, Smad3 and Smad7. Our studies in mouse C3H10T1/2 fibroblasts suggested that a number of TGF-β-induced genes that regulate matrix turnover are selectively regulated by HDACs. Blockade of HDAC activity with trichostatin A (TSA) abrogated the induction of a disintegrin and metalloproteinase 12 (Adam12) and tissue inhibitor of metalloproteinases-1 (Timp-1) genes by TGF-β, whereas plasminogen activator inhibitor-1 (Pai-1) expression was unaffected. Analysis of the activation of cell signalling pathways demonstrated that TGF-β induced robust ERK and PI3K activation with delayed kinetics compared to the phosphorylation of Smads. The TGF-β induction of Adam12 and Timp-1 was dependent on such non-Smad signalling pathways and, importantly, HDAC inhibitors completely blocked their activation without affecting Smad signalling. Analysis of TGF-β-induced Adam12 and Timp-1 expression and ERK/PI3K signalling in the presence of semiselective HDAC inhibitors valproic acid, MS-275 and apicidin implicated a role for class I HDACs. Furthermore, depletion of HDAC3 by RNA interference significantly down-regulated TGF-β-induced Adam12 and Timp-1 expression without modulating Pai-1 expression. Correlating with the effect of HDAC inhibitors, depletion of HDAC3 also blocked the activation of ERK and PI3K by TGF-β. Collectively, these data confirm that HDACs, and in particular HDAC3, are required for activation of the ERK and PI3K signalling pathways by TGF-β and for the subsequent gene induction dependent on these signalling pathways.

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Section: Histone Deacetylases Regulate a Subset Of Tgf-β-induced Genessupporting

confidence: 76%

Section: Hdac3 Regulates the Tgf-β Induction Of Activator Proteinssupporting

confidence: 49%

“…We have also found that the expression of a number of TGF-β-induced AP-1 proteins is repressed by TSA (Young et al, 2005 and Supp. Fig.…”

Section: Hdac3 Regulates the Tgf-β Induction Of Activator Proteinsmentioning

confidence: 75%

Section: Histone Deacetylases Regulate a Subset Of Tgf-β-induced Genesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Barter¹,

Pybus²,

Litherland³

et al. 2010

Matrix Biology

Self Cite

View full text Add to dashboard Cite

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Histone Deacetylase Inhibitors as a Therapeutic Modality in Multiple Sclerosis

Gray

2009

The Epigenetics of Autoimmune Diseases

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Dermatopontin: A potential predictor for metastasis of human oral cancer

Yamatoji

Kasamatsu

Kouzu

et al. 2011

Intl Journal of Cancer

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Dermatopontin (DPT), a component of the extracellular matrix (ECM), is involved in promotion of cellular adhesion and ECM assembly activities. However, the role of DPT in the pathogenesis of carcinoma is unclear. We evaluated DPT expression in human oral cancer and its possible roles including cellular adhesion and invasiveness. We first investigated the DPT mRNA and protein expression status in human oral squamous cell carcinoma (OSCC)-derived cells. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analysis detected frequent downregulation of DPT in OSCC-derived cells compared to human normal oral keratinocytes. To assess the epigenetic regulation of DPT, OSCC-derived cells were treated with a histone deacetylase inhibitor, sodium butyrate (NaB). NaB restored the DPT expression in OSCCderived cells. DPT-overexpressed cells were examined whether DPT could contribute to cellular adhesion and invasiveness. Markedly, increased adhesion and decreased invasiveness in DPT-overexpressed cells were found compared to mocktransfected cells. Adhesion of DPT-overexpressed cells was inhibited by a3b1 integrin functional blocking antibody. OSCCderived cells treated with NaB also decreased invasiveness. The expression status of DPT in primary OSCCs (n 5 97) was analyzed and compared to clinicopathological behavior. DPT expression in primary OSCCs was significantly lower (p < 0.05) than in the normal counterparts and was correlated significantly (p < 0.05) with regional lymph node metastasis. Our data provided strong evidence that downregulation of DPT is a characteristic event in OSCCs and that DPT was correlated with cellular adhesion and invasiveness. Therefore, DPT might play an important role in regulating tumor invasion and metastasis.Tumor invasion and metastasis associated with neoplastic progression are major causes of cancer deaths, including oral squamous cell carcinoma (OSCC).1 Improvements of prognosis in OSCC depend on the elucidation of the biologic and molecular mechanisms underlying metastatic diseases. In this context, the extracellular matrix (ECM) has been shown to play a pivotal role in metastasis.2 The invasiveness and metastatic processes occur through interactions between the cancer cells and the ECM, which is a complex structural entity that surrounds and supports the cells within living systems.

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Differential effects of histone deacetylase inhibitors on phorbol ester‐ and TGF‐β1 induced murine tissue inhibitor of metalloproteinases‐1 gene expression

Cited by 27 publications

References 48 publications

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

HDAC-mediated control of ERK- and PI3K-dependent TGF-β-induced extracellular matrix-regulating genes

Histone Deacetylase Inhibitors as a Therapeutic Modality in Multiple Sclerosis

Dermatopontin: A potential predictor for metastasis of human oral cancer

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