Transcription factors GATA-4 and GATA-6, and their potential downstream effectors in ovarian germ cell tumors.
Ovarian germ cell tumors (GCTs) are histologically heterogeneous neoplasms originating from activated germ cells, the oocyte stem cells. These rare tumors often contain many different tissues mixed together, and malignant components are occasionally hidden within benign tissues thus complicating the diagnosis. The reasons for the variable differentiation of germ cells are still largely unknown. As transcription factors GATA-4 and GATA-6 as well as their downstream factors (e.g. HNF-4, BMP-2 and Ihh) are essential for normal yolk sac development, we studied their expression in 19 ovarian GCTs. Endodermal markers were expressed distinctively in different GCT types. The malignant endoderm in yolk sac tumors expressed all factors of endodermal development included in the study. Dysgerminomas, on the contrary, expressed only GATA-4 and, in a minority of cases, Ihh and BMP-2. The results suggest that GATA-4 and GATA-6 detected in the ovarian GCTs have retained their normal function. The fact that GATA-6 and HNF-4 are expressed exclusively in endodermal tissues indicates that these transcription factors play a role in the differentiation of germ cells towards the endodermal phenotype. Analysis of the nuclear transcription factors in tumor tissue could serve as a new informative diagnostic tool for ovarian GCTs.
Mannisto
Susanna
S
Program for Developmental and Reproductive Biology, Biomedicum, University of Helsinki, Helsinki, Finland.
Butzow
Ralf
R
Salonen
Jonna
J
Leminen
Arto
A
Heikinheimo
Oskari
O
Heikinheimo
Markku
M
D000293:Adolescent; D000328:Adult; D002471:Cell Transformation, Neoplastic; D002648:Child; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D005260:Female; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; D020869:Gene Expression Profiling; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000503:physiopathology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D014157:Transcription Factors