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PMID: 18405344 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

BMC gastroenterology ·Vol. 8 ·2008-04-11 ·Pages 9

Haveri H, Westerholm-Ormio M, Lindfors K, Mäki M, Savilahti E, Andersson LC, Heikinheimo M

Abstract

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. 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. 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. 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.

MeSH Terms
Adenocarcinoma/genetics,pathology Adenoma/genetics,pathology Adolescent Adult Aged Barrett Esophagus/genetics,pathology Biopsy Child Child, Preschool Colonic Neoplasms/genetics,pathology Esophagus/metabolism,pathology GATA4 Transcription Factor/genetics,metabolism GATA6 Transcription Factor/genetics,metabolism Gastric Mucosa/metabolism,pathology Gastritis/genetics,pathology Gastritis, Atrophic/genetics,pathology Humans Immunohistochemistry Infant Middle Aged RNA, Messenger/analysis Rectal Neoplasms/genetics,pathology
Chemicals
GATA4 Transcription Factor GATA6 Transcription Factor RNA, Messenger
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Haveri Hanna
Children's Hospital, University of Helsinki, Helsinki, Finland. [email protected]
Westerholm-Ormio Mia
Lindfors Katri
Mäki Markku
Savilahti Erkki
Andersson Leif C
Heikinheimo Markku
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Article Info
Journal
BMC gastroenterology
Abbr.
BMC Gastroenterol
ISSN
1471-230X
DOI
10.1186/1471-230X-8-9
Email
[email protected]
Published
2008-04-11
Epub
2008-00-11
Pages
9
Language
English
Region
England
NLM ID
100968547
PMCID
PMC2323380
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-230X-8-9 PMC Full Text View journal details
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