Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh), in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and GATA-6 in the normal gastrointestinal mucosa. Furthermore, GATA-4, GATA-6 and Ihh expression is altered in premalignant dysplastic lesions and reduced in overt cancer.BioMed Central Open acces

In Crohn's Disease, Anti-TNF-α Treatment Changes the Balance between Mucosal IL-17, FOXP3, and CD4 Cells

Peer reviewe

Lasten kliinisesti eriytyneen oireyhtymän ja MS-taudin erityispiirteet

Peer reviewe

Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa-2

') was used to detect neuroendocrine cells and staining for H+/K+-ATPase α (HK) (blue-greyish cytoplasmic staining in B and B' to detect parietal cells. The samples were double-stained for GATA-4 (G4) or GATA-6 (G6) (brown nuclear staining). The GATA proteins are not expressed in the neuroendocrine cells of the stomach, duodenum, or colon (A, A', C, C', F and F' respectively; arrowheads). GATA-4 is detected in the H+/K+-ATPase α presenting parietal cells (B). GATA-6 is positive in approximately two thirds of the parietal cells positive for H+/K+-ATPase α (B', arrowheads). Some duodenal goblet cells, stained deep blue by the Alcian blue method (Alc) (D'), and most Paneth cells are positive for GATA-6 (E', arrowhead) showing no immunoreactivity for GATA-4 (D and E, arrowheads). Scale bar = 50 μm.<p><b>Copyright information:</b></p><p>Taken from "Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa"</p><p>http://www.biomedcentral.com/1471-230X/8/9</p><p>BMC Gastroenterology 2008;8():9-9.</p><p>Published online 11 Apr 2008</p><p>PMCID:PMC2323380.</p><p></p

Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa-4

TA-4 mRNA expression is strongest in the middle and superficial layers (A-A'), while GATA-6 mRNA expression is most abundant in the basal two thirds of the mucosa (B-B'). In the duodenum, the enterocytes lining the villi are strongly positive for GATA-4 (C-C'), whereas the GATA-6 signal is more diffuse (D and D'). GATA-4 is no longer detected in the ileum (E and E') and colon (G and G'); the bright lining on the surface of the mucosa is due to tissue autofluorescence (E-E' and G-G'). In contrast, GATA-6 expression is prominent both in the small (D, D', F, and F') and large intestine (H and H') presenting positivity in the surface and crypt enterocytes, and the cells of the lamina propria (D-D', F-F', and H-H'). Scale bar = 50 μm. Abbreviations: STO = stomach, DUO = duodenum, ILE = ileum, COL = colon.<p><b>Copyright information:</b></p><p>Taken from "Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa"</p><p>http://www.biomedcentral.com/1471-230X/8/9</p><p>BMC Gastroenterology 2008;8():9-9.</p><p>Published online 11 Apr 2008</p><p>PMCID:PMC2323380.</p><p></p

Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa-3

And A", respectively). The insets in A, A' and A" represent magnifications of cardiac glands. GATA-4 and GATA-6 are strongly expressed in neuroendocrine cell hyperplasia (B and B', respectively) in contrast to no or little expression of Ihh (B"). GATA-4 is detected neither in colon adenomas (C) nor carcinomas (D). The expressions of GATA-6 and Ihh are weak in adenomas, but enhanced in high grade dysplasias (C' and C" with insets). Little GATA-6 is found in the carcinoma tissue (D'). Ihh is not present in colon carcinoma (D"). Scale bar = 50 μm.<p><b>Copyright information:</b></p><p>Taken from "Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa"</p><p>http://www.biomedcentral.com/1471-230X/8/9</p><p>BMC Gastroenterology 2008;8():9-9.</p><p>Published online 11 Apr 2008</p><p>PMCID:PMC2323380.</p><p></p