FR901228, an inhibitor of histone deacetylases, increases the cellular responsiveness to IL-6 type cytokines by enhancing the expression of receptor proteins

Blanchard, Frédéric; Kinzie, Erin; Wang, Yanping; Duplomb, Laurence; Godard, Anne; Held, William A.; Asch, Bonnie B.; Baumann, Heinz

doi:10.1038/sj.onc.1205777

Cited by 31 publications

(53 citation statements)

References 58 publications

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“…histone deacetylation, as a major regulatory mechanism responsible for OSMRb silencing and OSM resistance. The OSMRb promoter structure thus appears similar to the one already described for the gp130 and LIFRa genes (Blanchard et al, 2002). The LIFRa and OSMRb genes are located within 500 kbp on chromosome 5 (in 5p13), suggesting a common ancestral gene, whereas the gp130 gene is located near them in 5q11.…”

Section: Osm Receptor Expression In Melanomamentioning

confidence: 51%

“…Indeed, these inhibitors can induce expression of several epigenetically silenced tumor suppressor genes, resulting in cell cycle arrest and differentiation (Jaenisch and Bird, 2003;Blanchard and Chipoy, 2005). Our data indicated that the promoters for gp130 or LIFRa can be epigenetically silenced in normal or transformed cells, concomitant with a defect in receptor expression and STAT signaling (Blanchard et al, 2002;Blanchard et al, 2003).…”

Section: Waf1mentioning

confidence: 89%

“…In previous studies conducted in numerous normal or transformed cells, such as hepatoma cells, gp130 or OSMRb downregulations were rarely observed, in contrast to the LIFRa gene that was frequently epigenetically silenced (Blanchard et al, 2002(Blanchard et al, , 2003. In stage III melanoma, both LIFRa and OSMRb were found frequently downregulated, but only the OSMRb recruitment correlated with OSM-mediated growth inhibition.…”

Section: Osm Receptor Expression In Melanomamentioning

confidence: 99%

“…One study showed that melanoma cells derived from advanced-stage lesions are often resistant to growth inhibition by OSM and that OSM resistance does not always correlate with IL-6 resistance (Lu et al, 1993), suggesting a defect in an OSM-specific pathway. We previously showed that responsiveness to IL-6-type cytokines can be increased by histone deacetylase (HDAC) or DNA methyltransferase inhibitors (Blanchard et al, 2002;Blanchard et al, 2003). Indeed, these inhibitors can induce expression of several epigenetically silenced tumor suppressor genes, resulting in cell cycle arrest and differentiation (Jaenisch and Bird, 2003;Blanchard and Chipoy, 2005).…”

Section: Waf1mentioning

confidence: 99%

“…Because we previously showed that gp130 and LIFRa expression can be regulated by epigenetic mechanisms in various cells (Blanchard et al, 2002;Blanchard et al, 2003), we asked whether the OSMRb gene could be similarly controlled in melanoma.…”

Section: Osm Receptor Expression In Melanomamentioning

confidence: 99%

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Loss of oncostatin M receptor β in metastatic melanoma cells

Lacreusette

Jm²,

et al. 2006

Oncogene

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Oncostatin M (OSM) is an interleukin-6 (IL-6) type cytokine originally described by its capacity to inhibit melanoma proliferation in vitro. Here, the mechanisms involved in resistance to growth inhibition by OSM were analysed for the first time on a large panel of metastatic melanoma cell lines. OSM resistance did not strictly correlate with IL-6, interferon-c or tumor necrosis factora resistance. Rather, it correlated with a specific loss of the OSM receptor-b (OSMRb) subunit, in conjunction with a lower level of histone acetylation in the OSMRb promoter region. Treatment of various OSM-resistant melanoma cells with the histone deacetylase inhibitor Trichostatin A increased activity and histone acetylation of the OSMRb promoter as well as expression of OSMRb mRNA and protein, allowing OSM to activate the signal transducer and activator of transcription 3 (STAT3) and to inhibit proliferation. Other defects associated with OSM resistance were identified at the level of OSMRb transcription or protein expression, as well as downstream of or parallel to STAT3 activation. Altogether, our results suggest a role for OSM in the prevention of melanoma progression and that metastatic melanoma cells could escape this growth control by the epigenetic silencing of OSMRb.

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Section: Osm Receptor Expression In Melanomamentioning

confidence: 51%

Section: Waf1mentioning

confidence: 89%

Section: Osm Receptor Expression In Melanomamentioning

confidence: 99%

Section: Waf1mentioning

confidence: 99%

Section: Osm Receptor Expression In Melanomamentioning

confidence: 99%

See 3 more Smart Citations

Loss of oncostatin M receptor β in metastatic melanoma cells

Lacreusette

Jm²,

et al. 2006

Oncogene

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Histone deacetylase inhibitors: Understanding a new wave of anticancer agents

Villar-Garea

Esteller

2004

Intl Journal of Cancer

240

193

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Cancer is as much an epigenetic disease as it is a genetic and cytogenetic disease. The discovery that drastic changes in DNA methylation and histone modifications are commonly found in human tumors has inspired various laboratories and pharmaceutical companies to develop and study epigenetic drugs. One of the most promising groups of agents is the inhibitors of histone deacetylases (HDACs), which have different biochemical and biologic properties but have a single common activity: induction of acetylation in histones, the key proteins in nucleosome and chromatin structure. One of the main mechanisms of action of HDAC inhibitors is the transcriptional reactivation of dormant tumor-suppressor genes, such as p21 WAF1 . However, their pleiotropic nature leaves open the possibility that their wellknown differentiation, cell-cycle arrest and apoptotic properties are also involved in other functions associated with HDAC inhibition. Many phase I clinical trials indicate that HDAC inhibitors appear to be well-tolerated drugs. Thus, the field is ready for rigorous biologic and clinical scrutiny to validate the therapeutic potential of these drugs. Our current data indicate that the use of HDAC inhibitors, probably in association with classical chemotherapy drugs or in combination with DNA-demethylating agents, could be promising for cancer patients.

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Differentiation of mouse embryonic stem cells into hepatocytes induced by a combination of cytokines and sodium butyrate

Zhou

Tan

et al. 2009

J of Cellular Biochemistry

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There is increasing evidence to suggest that embryonic stem cells (ESCs) are capable of differentiating into hepatocytes in vitro. In this study, we used a combination of cytokines and sodium butyrate in a novel three-step procedure to efficiently direct the differentiation of mouse ESCs into hepatocytes. Mouse ESCs were first differentiated into definitive endoderm cells by 3 days of treatment with Activin A. The definitive endoderm cells were then differentiated into hepatocytes by the addition of acidic fibroblast growth factor (aFGF) and sodium butyrate to the culture medium for 5 days. After 10 days of further in vitro maturation, the morphological and phenotypic markers of hepatocytes were characterized using immunohistochemistry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, the cells were tested for functions associated with mature hepatocytes, including glycogen storage and indocyanine green uptake and release, and the ratio of hepatic differentiation was determined by counting the percentage of albumin-positive cells. In the presence of medium containing cytokines and sodium butyrate, numerous epithelial cells resembling hepatocytes were observed, and approximately 74% of the cells expressed the hepatic marker, albumin, after 18 days in culture. RT-PCR analysis and immunohistochemistry showed that these cells expressed adult liver cell markers, and had the abilities of glycogen storage and indocyanine green uptake and release. We have developed an efficient method for directing the differentiation of mouse ESCs into cells that exhibit the characteristics of mature hepatocytes. This technique will be useful for research into the molecular mechanisms underlying liver development, and could provide a source of hepatocytes for transplantation therapy and drug screening.

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FR901228, an inhibitor of histone deacetylases, increases the cellular responsiveness to IL-6 type cytokines by enhancing the expression of receptor proteins

Cited by 31 publications

References 58 publications

Loss of oncostatin M receptor β in metastatic melanoma cells

Loss of oncostatin M receptor β in metastatic melanoma cells

Histone deacetylase inhibitors: Understanding a new wave of anticancer agents

Differentiation of mouse embryonic stem cells into hepatocytes induced by a combination of cytokines and sodium butyrate

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