Transcription Factors GATA-4 and GATA-6, and their Potential Downstream Effectors in Ovarian Germ Cell Tumors

Vol. 26, No. 5, 2005

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Research Article

Transcription Factors GATA-4 and GATA-6, and their Potential Downstream Effectors in Ovarian Germ Cell Tumors
Susanna Mannisto^{a, b}, Ralf Butzow^{c, d}, Jonna Salonen^d, Arto Leminen^d, Oskari Heikinheimo^d, Markku Heikinheimo^{a, b}

^aProgram for Developmental and Reproductive Biology, Biomedicum, and Departments of
^bPediatrics,
^cPathology, and
^dObstetrics and Gynecology, University of Helsinki, Helsinki, Finland

Address of Corresponding Author

Tumor Biol 2005;26:265-273 (DOI: 10.1159/000087565)

Key Words

Dysgerminoma
GATA-4
GATA-6
Germ cell tumor
Teratomas
Transcription factor
Yolk sac tumor

Abstract

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.

Author Contacts

Markku Heikinheimo, MD, PhD
Program for Developmental and Reproductive Biology
Biomedicum Helsinki, Room B525b, PO Box 63 (Haartmaninkatu 8)
FI-00014 University of Helsinki (Finland)
Tel. +358 9 4717 1977, Fax +358 9 4717 1947, E-Mail markku.heikinheimo@helsinki.fi

Article Information

Received: February 8, 2005
Accepted after revision: May 10, 2005
Published online: August 17, 2005
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 2, Number of References : 36

Medline Abstract (ID 16110260)

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