GATA4 and GATA5 are Potential Tumor Suppressors and Biomarkers in Colorectal Cancer

Hellebrekers, Debby M.E.I.; Lentjes, Marjolein H.F.M.; Bosch, Sandra M. van den; Melotte, Veerle; Wouters, Kristien; Daenen, Kathleen L.J.; Smits, Kim M.; Akiyama, Yoshimitsu; Yuasa, Yasuhito; Sanduleanu, Silvia; Bakker, Carolina A.J. Khalid-de; Jonkers, Daisy; Weijenberg, Matty P.; Louwagie, Joost; Criekinge, Wim Van; Carvalho, Beatriz; Meijer, Gerrit A.; Baylin, Stephen B.; Herman, James G.; Bruïne, Adriaan P. de; Engeland, Manon van

doi:10.1158/1078-0432.ccr-09-0055

Cited by 168 publications

(154 citation statements)

References 29 publications

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“…Functionally, they activate the promoter of tumor suppressor genes and serve as tumor suppressors, the lost expression of which accelerates the development of colon cancer. For example, colon cells with GATA4 and 5 expression had reduced colony formation, proliferation, migration, invasion and anchor growth (12). In a previous study, GATA4 and GATA5 expression was lost in HepG2 cells and GATA4 and GATA5 transfection experiments inhibited tumor cell growth and colony formation, but induces tumor cell apoptosis.…”

Section: A B C D Ementioning

confidence: 88%

“…The present study also demonstrated that GATA5 promoter methylation was more frequent in older patients, indicating that GATA5 promoter methylation may be an independent risk factor for older HCC patients. GATA4 and 5, as transcription factors, are involved in normal cell growth and also in adrenal gland, lung, ovary and colorectal cancer development (12). Functionally, they activate the promoter of tumor suppressor genes and serve as tumor suppressors, the lost expression of which accelerates the development of colon cancer.…”

Section: A B C D Ementioning

confidence: 99%

“…In adults, GATA4 and GATA5 regulate epithelial cell differentiation (10,11). However, altered expression of GATA4 and GATA5 proteins is associated with tumorigenesis in certain organs and tissues, including gastric and colon cancer; thus, GATA4 and GATA5 may act as putative tumor suppressor genes (11,12). A previous study revealed that GATA4 and GATA5 expression was lost in ovarian and gastric cancer, and demonstrated that chromosomal regions of GATA4 (8p23.1-p22) and GATA5 (20q13.2-q13.3) loci were frequently deleted in various types of human cancer (13).…”

Section: Introductionmentioning

confidence: 99%

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Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

et al. 2015

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Abstract. GATA5 is a transcription factor that is capable of suppressing the development of various types of human cancer. The present study investigated the expression of GATA5 and GATA4, and examined their roles in the proliferation and colony formation ability of hepatocellular carcinoma (HCC) tissues and cells. The GATA4 and GATA5 expression levels and gene promoter methylation of HCC tissue samples from 38 patients and HCC cell lines were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP), respectively. The effects of GATA4 and GATA5 overexpression on the proliferation and colony forming ability of HCC cells were also assessed using cell viability and colony formation assays. A luciferase reporter assay was utilized to investigate the transcriptional interaction of GATA4 and GATA5 with canonical Wnt signaling. The results indicated that the expression levels of GATA4 and GATA5 were lost or reduced following methylation of gene promoters in HCC tissues and cell lines. Treatment with a demethylating agent, 5-aza-2'-deoxycytidine (5-AZA), restored GATA4 and GATA5 expression in HCC cell lines. Furthermore, methylation of the GATA5 promoter was observed to be associated with the age of patients exhibiting HCC. Restoration of GATA4 and GATA5 expression inhibited colony formation and induced apoptosis of HCC cells in vitro. The present study concluded that the expression levels of GATA4 and GATA5 were reduced in HCC tissues and cell lines. Treatment with 5-AZA restored GATA4 and GATA5 expression in HCC cell lines, suppressing tumor cell growth and colony formation, as well as inducing apoptosis.

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Section: A B C D Ementioning

confidence: 88%

Section: A B C D Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

et al. 2015

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“…For example, promoter hypermethylation is associated with the silencing of various cancer-related genes (14,15), and aberrant methylation of the CpG islands of genes in stool and serum/plasma can be used as a molecular marker for detection of colorectal tumors (16)(17)(18)(19)(20). On the contrary, because DNA methylation is an early event (21)(22)(23), it does not enable one to distinguish between premalignant lesions and invasive tumors.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Alteration of DNA in Mucosal Wash Fluid Predicts Invasiveness of Colorectal Tumors

Kamimae

Yamamoto

Yamano

et al. 2011

Cancer Prevention Research

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Although conventional colonoscopy is considered the gold standard for detecting colorectal tumors, accurate staging is often difficult because advanced histology may be present in small colorectal lesions. We collected DNA present in mucosal wash fluid from patients undergoing colonoscopy and then assessed the methylation levels of four genes frequently methylated in colorectal cancers to detect invasive tumors. We found that methylation levels in wash fluid were significantly higher in patients with invasive than those with noninvasive tumors. Cytologic and K-ras mutation analyses suggested that mucosal wash fluid from invasive tumors contained greater numbers of tumor cells than wash fluid from noninvasive tumors. Among the four genes, levels of mir-34b/c methylation had the greatest correlation with the invasion and showed the largest area under the receiver operating characteristic curve (AUC ¼ 0.796). Using cutoff points of mir-34b/c methylation determined by efficiency considerations, the sensitivity/specificity were 0.861/0.657 for the 13.0% (high sensitivity) and 0.765/0.833 for the 17.8% (well-balanced) cutoffs. In the validation test set, the AUC was also very high (0.915), the sensitivity/specificity were 0.870/0.875 for 13.0% and 0.565/0.958 for 17.8%. Using the diagnostic tree constructed by an objective algorithm, the diagnostic accuracy of the invasiveness of colorectal cancer was 91.3% for the training set and 85.1% for the test set. Our results suggest that analysis of the methylation of DNA in mucosal wash fluid may be a good molecular marker for predicting the invasiveness of colorectal tumors. Cancer Prev Res; 4(5); 674-83. Ó2011 AACR.

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“…Moreover, methylation markers can be useful for early detection of cancer. For instance, presence of TFPI2 or GATA4 methylation in stool DNA has reasonably high predictive value of colorectal cancer and can be used as a non-invasive screening tool coupled with conventional screening methods [165,166].…”

Section: Biomarker Developmentmentioning

confidence: 99%

Cancer epigenetics: linking basic biology to clinical medicine

2011

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Cancer evolution at all stages is driven by both epigenetic abnormalities as well as genetic alterations. Dysregulation of epigenetic control events may lead to abnormal patterns of DNA methylation and chromatin configurations, both of which are critical contributors to the pathogenesis of cancer. These epigenetic abnormalities are set and maintained by multiple protein complexes and the interplay between their individual components including DNA methylation machinery, histone modifiers, particularly, polycomb (PcG) proteins, and chromatin remodeling proteins. Recent advances in genome-wide technology have revealed that the involvement of these dysregulated epigenetic components appears to be extensive. Moreover, there is a growing connection between epigenetic abnormalities in cancer and concepts concerning stem-like cell subpopulations as a driving force for cancer. Emerging data suggest that aspects of the epigenetic landscape inherent to normal embryonic and adult stem/ progenitor cells may help foster, under the stress of chronic inflammation or accumulating reactive oxygen species, evolution of malignant subpopulations. Finally, understanding molecular mechanisms involved in initiation and maintenance of epigenetic abnormalities in all types of cancer has great potential for translational purposes. This is already evident for epigenetic biomarker development, and for pharmacological targeting aimed at reversing cancerspecific epigenetic alterations.

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GATA4 and GATA5 are Potential Tumor Suppressors and Biomarkers in Colorectal Cancer

Cited by 168 publications

References 29 publications

Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

Loss of GATA5 expression due to gene promoter methylation induces growth and colony formation of hepatocellular carcinoma cells

Epigenetic Alteration of DNA in Mucosal Wash Fluid Predicts Invasiveness of Colorectal Tumors

Cancer epigenetics: linking basic biology to clinical medicine

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