title: The developmental transcription factor Gata4 is overexpressed in pancreatic ductal adenocarcinoma.
abstract: GATA4 is a transcription factor that plays a role in regulating the normal development of many mesoderm and endoderm derived tissues, including the pancreas. Silencing of GATA4 mRNA expression by promoter methylation has been implicated in carcinogenesis of the ovary, lung and colorectum. By contrast, GATA4 mRNA expression is upregulated in pancreatic cancer cell lines and tissues. To further clarify the relationship of GATA4 to pancreatic cancer, we immunolabeled 90 samples of pancreatic ductal adenocarcinoma using a GATA4 specific monoclonal antibody. Both the intensity and percent of labeling was recorded for each carcinoma and correlated to the clinic opathologic features available for each patient. Samples of normal adult (n=26) and fetal pancreatic tissue (n=8) were also immunolabeled for comparison to expression patterns in pancreatic carcinoma tissues. Immunolabeling for GATA4 indicated robust nuclear expression in developing acini in fetal pancreatic tissues, consistent with the role of GATA4 in embryologic development, and in mature pancreatic acinar epithelium. Immunolabeling for GATA4 was also noted within normal duct epithelial cells, although it was always lesser in intensity than for acinar cell nuclei in the same section. Positive GATA4 immunolabeling was seen in 61/90 (68%) infiltrating pancreatic cancers of which 27/90 (30%) showed strong positive labeling. While there was no relationship among GATA4 and patient age, race or pathologic features, we did find a significant association among strong positive labeling and female gender (p=0.01). These findings support previous studies implicating GATA4 in pancreatic cancer and offer new avenues for investigation into this aggressive tumor type.
authors.affiliation: Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Karafin
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Cummings
authors.forename: Baojin
authors.initials: B
authors.lastname: Fu
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus; D050991:GATA4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005865:Gestational Age; D006801:Humans; D008297:Male; D010179:Pancreas / Q000196:embryology / Q000378:metabolism / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016577:Pancreaticoduodenectomy; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D012333:RNA, Messenger