Disease relevance of GATA5

• Our findings suggest that GATA5 interacts with the +331G/A polymorphism to stimulate hPR-B expression in mammary cells, which may contribute to breast cancer susceptibility [1].
• GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer [2].
• In 63 cases of primary lung cancers, GATA-4 and GATA-5 promoter methylation was detected in (42 of 63) 67% and (26 of 63) 41%, respectively [3].
• Loss of GATA-4 and GATA-5 has been reported in human gastric and colon cancer [4].
• GATA-4 and GATA-5 expression was absent in most esophageal cancer cell lines, but was restored upon treatment with the demethylating agent 5-aza-2'-deoxycytidine [4].

High impact information on GATA5

• Expression of exogenous GATA-5 overrides methylation at the downstream promoters to activate the target genes [2].
• GATA5 activation of the progesterone receptor gene promoter in breast cancer cells is influenced by the +331G/A polymorphism [1].
• The results indicate that GATA5 is induced at an early stage of endothelial-endocardial differentiation prior to expression of such early endocardial markers as Tie2 and ErbB3 [5].
• Physical interaction between GATA-5 and hepatocyte nuclear factor-1alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter [6].
• RESULTS: Complete methylation was detected by methylation-specific PCR for both GATA-4 and GATA-5 in four cell lines (H358, DMS-53, A549, and H1299), all of which had no expression by reverse transcription-PCR analysis [3].

Biological context of GATA5

• This finding was relevant because GATA5 bound the site adjacent to the +331G/A polymorphism, and activated the hPR (-711 to +822)-luciferase reporter plasmid in breast cancer cells [1].
• GATA-4, GATA-5, and GATA-6 are endodermal zinc-finger transcription factors that activate numerous enterocytic genes [7].
• However, at saturated levels of GATA-4, additional transgene activation was achieved by adding GATA-5 expression construct, and vice versa [7].
• Transcription factor GATA-5 selectively up-regulates mucin gene expression [8].
• Reporter gene assays were employed to analyze the effect of GATA-5 on the promoter activity of mucin genes [8].

Anatomical context of GATA5

• The expression of GATA4 and GATA5 was undetectable in four and six cell lines, respectively, whereas the majority of the cell lines expressed GATA6 abundantly [9].
• GATA-4/-5 promoter methylation was not detected in normal esophageal mucosa, but GATA-4 methylation was present in 27 of 44 (61%) squamous carcinomas and 31 of 44 (71%) adenocarcinoma of the esophagus, while GATA-5 methylation was present in 14 of 44 (32%) squamous carcinomas and 24 of 44 (55%) adenocarcinoma of the esophagus [4].
• CONCLUSIONS: These findings indicate that GATA-5 may play important roles in the regulation of mucin expression and gastrointestinal epithelial cell differentiation [8].

Regulatory relationships of GATA5

• By means of luciferase assay, GATA-5 was found to activate the promoters of the human MUC2 and MUC4 genes [8].

Other interactions of GATA5

• Differential activation of intestinal gene promoters: functional interactions between GATA-5 and HNF-1 alpha [10].
• Normal tissues showed significantly lower frequencies of promoter methylation of APC, p16(INK4A), GATA-4, and GATA-5 (P-values: 0.02, 0.02, 1.1x10(-5) and 0.008 respectively) [11].

Analytical, diagnostic and therapeutic context of GATA5

• GATA-5 expression was confirmed by Western blot analysis [8].

References