DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor

Blanchard, Frédéric; Tracy, Erin; Smith, Joseph F.; Chattopadhyay, Souvik; Wang, Yanping; Held, William A.

doi:10.1016/j.hep.2003.09.029

Cited by 17 publications

(19 citation statements)

References 40 publications

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“…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: 74%

“…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: 76%

“…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: 74%

Section: Waf1mentioning

confidence: 76%

Section: Waf1mentioning

confidence: 99%

Section: Osm Receptor Expression In Melanomamentioning

confidence: 99%

See 2 more Smart Citations

Loss of oncostatin M receptor β in metastatic melanoma cells

Lacreusette

Jm²,

et al. 2006

Oncogene

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“…There was no evidence from our own demethylation experiments in epithelial tumor cell lines in vitro [4].…”

Section: Introductionmentioning

confidence: 64%

Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

2008

Self Cite

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We have demonstrated that constitutive signal transducer and activator of transcription (STAT) 3 activity, observed in approximately 50% of acute myeloid leukemia (AML) cases, is associated with adverse treatment outcome. Constitutive STAT3 activation may result from the expression of oncogenic protein tyrosine kinases or from autocrine stimulation by hematopoietic growth factors. These causes are generally neither necessary nor sufficient for leukemogenesis; additional transforming events or growth stimulatory processes are needed. Here we review the literature addressing epigenetic regulation as a mechanism controlling STAT3 signaling in AML. A better understanding of mechanisms of dysregulation of STAT signaling pathways may serve as a basis for designing novel therapeutic strategies that target these pathways in leukemia cells.

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DNA methylation of cancer genome

Cheung

Lee

Rennert

et al. 2009

Birth Defects Research Pt C

127

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DNA methylation plays an important role in regulating normal development and carcinogenesis. Current understanding of the biological roles of DNA methylation is limited to its role in the regulation of gene transcription, genomic imprinting, genomic stability, and X chromosome inactivation. In the past 2 decades, a large number of changes have been identified in cancer epigenomes when compared with normals. These alterations fall into two main categories, namely, hypermethylation of tumor suppressor genes and hypomethylation of oncogenes or heterochromatin, respectively. Aberrant methylation of genes controlling the cell cycle, proliferation, apoptosis, metastasis, drug resistance, and intracellular signaling has been identified in multiple cancer types. Recent advancements in whole-genome analysis of methylome have yielded numerous differentially methylated regions, the functions of which are largely unknown. With the development of high resolution tiling microarrays and high throughput DNA sequencing, more cancer methylomes will be profiled, facilitating the identification of new candidate genes or ncRNAs that are related to oncogenesis, new prognostic markers, and the discovery of new target genes for cancer therapy. †

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DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor

Cited by 17 publications

References 40 publications

Loss of oncostatin M receptor β in metastatic melanoma cells

Loss of oncostatin M receptor β in metastatic melanoma cells

Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

DNA methylation of cancer genome

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