Hypermethylation of the GATA Genes in Lung Cancer

Guo, Mingzhou; Akiyama, Yoshimitsu; House, Michael G.; Hooker, Craig M.; Heath, E.; Gabrielson, Edward; Yang, Stephen C.; Han, Yu; Baylin, Stephen B.; Herman, James G.; Brock, Malcolm V.

doi:10.1158/1078-0432.ccr-04-1140

Cited by 115 publications

(98 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Loss of GATA4 expression is observed in several cancers, such as squamous cell, ovarian and lung cancers (Capo-chichi et al, 2003;Guo et al, 2004Guo et al, , 2006Caslini et al, 2006). In addition, GATA4 loss by deletion of chromosome 8p or mutation has been implicated as a predisposing factor in patients with congenital heart disease (Garg et al, 2003;Reamon-Buettner et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

et al. 2009

View full text Add to dashboard Cite

The GATA transcription factors consist of six family members, which bind to the consensus DNA-binding element, W-GATA-R, and are poorly characterized in the central nervous system (CNS). Using retroviral gene trapping on transgenic mouse glioma models, we identified GATA6 to be a novel tumor suppressor gene in glioblastoma multiforme. We now show GATA4, a family member of GATA6, to be expressed in the neurons and glia of normal murine and human embryonic and adult CNS. Silencing GATA4 in normal astrocytes did not alter their growth properties. In contrast, knockdown of Gata4 in p53 null non-transformed murine astrocytes induced transformation, with increased proliferation and resistance to chemotherapy or radiation-induced apoptosis. Furthermore, GATA4 expression was lost in a panel of human malignant astrocytoma cell lines. GATA4 overexpression in normal human and murine astrocytes resulted in a cell cycle block in G1 phase, with increased apoptosis. Mechanistically, GATA4 was a transcriptional inducer of the cyclin-dependent kinase inhibitor, p15INK4B, leading to the attenuation of cyclin D1. GATA4 expression was also induced by transforming growth factor-b, leading to the inhibition of astrocyte proliferation. Collectively, we show that GATA4 is expressed in the embryonic and adult CNS and acts as a negative regulator of astrocyte proliferation and growth.

show abstract

Section: Discussionmentioning

confidence: 99%

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

et al. 2009

View full text Add to dashboard Cite

show abstract

“…RNA (2 µg) was subjected to first strand cDNA synthesis, and subsequently 1 µl cDNA from the RT reaction was subjected to PCR amplification in a total reaction volume of 25 µl. PCR amplification was performed using primer sets derived from the published GATA4 and GATA5 gene sequences (22). PCR conditions were set to 94˚C for 1 min, 64˚C for 1 min and 72˚C for 90 sec for 3 cycles and 94˚C for 1 min, 61˚C for 1 min and 72˚C for 90 sec for additional 3 cycles, and 94˚C for 1 min, 58˚C for 1 min, and 72˚C for 90 sec for final 3 cycles and then 94˚C for 1 min, 55˚C for 1 min, and 72˚C for 90 sec for 23 cycles and final 72˚C extension for 7 min.…”

Section: Rna Isolation and Semi-quantitative Reverse Transcription-pomentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

“…This protein may bind to the hypomethylated region of the GATA4 promoter, and thus regulate its expression, or even act as a partner in metastasis development. Although controversial, hypermethylation of GATA4 in lung cancer has been reported (18,26). A study from Guo and colleagues on the methylation of GATA genes in lung cancer used several lung cancer cell lines revealing GATA4 silencing by hypermethylation in most of the tested cells, including A549 (26).…”

Section: Myc Induces Gata4 Promoter Demethylationmentioning

confidence: 99%

“…Although controversial, hypermethylation of GATA4 in lung cancer has been reported (18,26). A study from Guo and colleagues on the methylation of GATA genes in lung cancer used several lung cancer cell lines revealing GATA4 silencing by hypermethylation in most of the tested cells, including A549 (26). Curiously, the only cells extracted from a metastatic tissue-H157-showed hypomethylation of their GATA4 promoter (26).…”

Section: Myc Induces Gata4 Promoter Demethylationmentioning

confidence: 99%

MYC-Induced Epigenetic Activation of GATA4 in Lung Adenocarcinoma

Castro

Breiling

Luetkenhaus

et al. 2013

Molecular Cancer Research

View full text Add to dashboard Cite

Human lung cancer is a disease with high incidence and accounts for most cancer-related deaths in both men and women. Metastasis is a common event in non-small cell lung carcinoma (NSCLC), diminishing the survival chance of the patients with this type of tumor. It has been shown that MYC is involved in the development of metastasis from NSCLC, but the mechanism underlying this switch remained to be identified. Here, we focus on GATA4 as a MYC target in the development of metastasis with origin in lung adenocarcinoma, the most common type of NSCLC. Epigenetic alterations at the GATA4 promoter level were observed after MYC expression in lung adenocarcinoma in vivo and in vitro. Such alterations include site-specific demethylation that accompanies the displacement of the MYC-associated zinc finger protein (MAZ) from the GATA4 promoter, which leads to GATA4 expression. Histone modification analysis of the GATA4 promoter revealed a switch from repressive histone marks to active histone marks after MYC binding, which corresponds to active GATA4 expression. Our results thus identify a novel epigenetic mechanism by which MYC activates GATA4 leading to metastasis in lung adenocarcinoma, suggesting novel potential targets for the development of antimetastatic therapy.

show abstract

Hypermethylation of the GATA Genes in Lung Cancer

Cited by 115 publications

References 33 publications

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

GATA4 is a regulator of astrocyte cell proliferation and apoptosis in the human and murine central nervous system

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

MYC-Induced Epigenetic Activation of GATA4 in Lung Adenocarcinoma

Contact Info

Product

Resources

About