Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer

Maat, Michiel F.G. de; Velde, Cornelis J.H. van de; Umetani, Naoyuki; Heer, Pieter de; Putter, Hein; Hoesel, Anneke Q. van; Meijer, Gerrit A.; Grieken, Nicole C.T. van; Kuppen, Peter J. K.; Bilchik, Anton J.; Tollenaar, Rob A.E.M.; Hoon, Dave S.B.

doi:10.1200/jco.2006.09.8921

Cited by 63 publications

(52 citation statements)

References 36 publications

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“…The use of the archival tissue array slides was exempt from approval by the Institutional Review Board at City of Hope Medical Center. TNBC, melanoma tumor, and normal skin tissue sections were prepared for IHC analysis as previously described (42), and were provided by the JWCI, with approval from the JWCI and Western Institutional Review Board. Immunofluorescent and IHC staining of tissue slides were performed as described previously (41).…”

Section: Methodsmentioning

confidence: 99%

Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation

Lee

Zhang

Herrmann

et al. 2012

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

196

202

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The mechanisms underlying hypermethylation of tumor-suppressor gene promoters in cancer is not well understood. Here, we report that lysine acetylation of the oncogenic transcription factor STAT3 is elevated in tumors. We also show that genetically altering STAT3 at Lys685 reduces tumor growth, which is accompanied by demethylation and reactivation of several tumor-suppressor genes. Moreover, mutating STAT3 at Lys685 disrupts DNA methyltransferase 1-STAT3 interactions in cultured tumor cells and in tumors. These observations are confirmed by treatment with an acetylation inhibitor, resveratrol. Furthermore, reduction of acetylated STAT3 in triple-negative breast cancer cells leads to demethylation and activation of the estrogen receptor-α gene, sensitizing the tumor cells to antiestrogens. Our results also demonstrate a correlation between STAT3 acetylation and methylation of estrogen receptor-α in melanoma, which predicts melanoma progression. Taken together, these results suggest a role of STAT3 acetylation in regulating CpG island methylation, which may partially explain aberrant gene silencing in cancer. These findings also provide a rationale for targeting acetylated STAT3 for chemoprevention and cancer therapy.

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Section: Methodsmentioning

confidence: 99%

Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation

Lee

Zhang

Herrmann

et al. 2012

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

196

202

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show abstract

“…24,25 Recent studies by our group and others on CRC have focused on tumor-related genes and epigenetic regulation by methylation status of specific CpG island sites in the promoter region. [26][27][28][29] However, these studies have not included stromal cells in the tumor microenvironment. Tumor microenvironment may provide the necessary conditions for tumor migration and invasion by fostering adaptation to the effects of tumor-associated epigenetic changes.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

Yoshimura

Nagahara²,

Kuo³

et al. 2011

Epigenetics

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“…Gastric cancer is usually detected at an advanced stage in many patients with lymph node invasion and metastasis. Despite a curative operation and postoperative adjuvant therapy, nearly 60% of those patients die of this fatal disease [22][23][24]. The total prognosis of gastric cancer is still poor [25].…”

mentioning

confidence: 99%

Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients

Zhang¹,

Jin²,

Yang³

et al. 2013

neo

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Human Hox genes (Homeobox) have crucial roles in development and differentiation, regulating numerous processes including apoptosis, receptor signalling, differentiation, motility and angiogenesis. Aberrant expression of Hoxc6 gene has been reported in several tumor tissues and cancer cell lines. The prognostic significance of Hoxc6 in gastric cancer remains largely unknown.This study was aimed to investigate the clinical significance of Hoxc6 in gastric cancer.Total RNA of paired tissue samples (n=25) and a tissue microarray containing 161 paired tissues from patients with gastric cancers at different stages were collected. Quantitative real-time PCR and immunochemistry assay were carried out to investigate the expression of Hoxc6.Hoxc6 mRNA was increased in gastric cancer tissues ( 16 of 25) compared with the adjacent normal mucosa (P<0.05). Immunohistochemical detection showed that expression of Hoxc6 was associated with the depth of tumor invasion (P<0.05). Patients with higher expression levels of Hoxc6 had a shorter overall survival rate (P<0.05).Hoxc6 might contribute to the progression of gastric carcinogenesis and may be a significant predictor of poor survival in patients with gastric cancer after curative operations.

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Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer

Abstract: Hypermethylation of COX-2 gene promoter was identified as an independent prognostic factor in gastric cancer patients. The results suggest promoter hypermethylation to be an important regulatory mechanism of COX-2 expression in gastric cancer and an important prognostic biomarker.

Cited by 63 publications

References 36 publications

Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation

Acetylated STAT3 is crucial for methylation of tumor-suppressor gene promoters and inhibition by resveratrol results in demethylation

Lymphovascular invasion of colorectal cancer is correlated to SPARC expression in the tumor stromal microenvironment

Upregulated Hoxc6 expression is associated with poor survival in gastric cancer patients

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