Transcription Factor GATA-6 Is Expressed in Malignant Endoderm of Pediatric Yolk Sac Tumors and in Teratomas

Siltanen, Susanna; Heikkilä, Päivi; Bielińska, Małgorzata; Wilson, David B.; Heikinheimo, Markku

doi:10.1203/01.pdr.0000081295.56529.e9

Cited by 19 publications

(15 citation statements)

References 32 publications

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“…This result supports our previous fi nding of the expression of GATA-4 and GATA-6 in pediatric yolk sac tumors [27,28] . However, no FOG-2 was detected in any of the YSTs by immunohistochemistry, suggesting that the action of GATA-4 is not modulated by its natural cofactor in these neoplasms.…”

Section: Discussionsupporting

confidence: 92%

“…Strong GATA-4 and GATA-6 expression was found in the malignant endoderm of all YSTs ( fi g. 2 b, c), consistent with our earlier reports on pediatric YSTs [27,28] . No GATA-4 cofactor FOG-2 was detectable by immunohistochemistry in any of the tumors ( fi g. 2 d).…”

Section: Markers For Endodermal Differentiation Are Widely Expressed supporting

confidence: 91%

“…The expression of GATA-4 is restricted to malignant yolk sac endoderm whereas GATA-6 is expressed in malignant yolk sac tumors and in those teratoma tissues that express this factor also during normal development [27,28] . We speculate that these factors may play a central role in the differentiation towards yolk sac tissue and could serve as clinical markers for this type of tissue in mixed GCTs.…”

Section: Introductionmentioning

confidence: 99%

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

Mannisto¹,

Bützow²,

Salonen³

et al. 2005

Tumor Biol

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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.

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Section: Discussionsupporting

confidence: 92%

Section: Markers For Endodermal Differentiation Are Widely Expressed supporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Mannisto¹,

Bützow²,

Salonen³

et al. 2005

Tumor Biol

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“…In line with this study, GATA-4 and GATA-6 expression has also been demonstrated in pediatric testicular as well as non-gonadal yolk sac tumors (27,28). Moreover, GATA-4 expression has been reported in adult ovarian and testicular yolk sac tumors (25,29).…”

Section: Discussionsupporting

confidence: 86%

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

Salonen

Meyts

Mannisto³

et al. 2010

European Journal of Endocrinology

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Objective: Testicular germ cell cancer is the most common malignancy among young males. The preinvasive precursor, carcinoma in situ testis (CIS), presumably originates from arrested and transformed fetal gonocytes. Given that GATA transcription factors have essential roles in embryonic and testicular development, we explored the expression of GATA-4, GATA-6, cofactor friend of GATA (FOG)-2, and downstream target genes during human testis development and addressed the question whether changes in this pathway may contribute to germ cell neoplasms. Methods: Fetal testis, testicular CIS, and overt tumor samples were analyzed by immunohistochemistry for GATA-4, GATA-6, FOG-2, steroidogenic factor 1 (NR5A1/SF1), anti-Mü llerian hormone/Mü llerianinhibiting substance (AMH), and inhibin-a (INHa). Results: GATA-4 was not expressed in normal germ cells, except for a subset of gonocytes at the 15th gestational week. The CIS cells expressed GATA-4 and GATA-6 heterogeneously, whereas most of the CIS cells expressed GATA-4 cofactor FOG-2. GATA target gene SF-1 was expressed heterogeneously in CIS cells, whereas INHa and AMH were mostly negative. Seminomas and yolk sac tumors were positive for GATA-4 and GATA-6, but mostly negative for FOG-2 and the GATA target genes. In contrast, pluripotent embryonal carcinomas and choriocarcinomas were GATA-4 and GATA-6 negative. Conclusions: Differential expression of the GATA-4 target genes suggested cell-specific functions of GATA-4 in the germ and somatic cells. The GATA-4 expression in early fetal gonocytes, CIS, and seminoma cells but the absence in more mature germ cells is consistent with the early fetal origin of CIS cells and suggests that GATA-4 is involved in early germ cell differentiation.

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“…The cytoplasmic staining observed does not appear to be the result of non-specific antibody adherence as no other antibody tested, including controls, resulted in such a staining pattern. While this observation is unusual for a GATA protein, there are other examples of cytoplasmic localization for mammalian GATA factors (Siltanen et al 2003, Nemer & Nemer 2003, Gillio-Meina et al 2003, Caramori et al 2001, Divine et al 2004. One very elegant study in ovarian epithelial cells, utilizing the same GATA-6 antibody as the studies described in this paper, has shown that GATA-6 can be found localized exclusively to the cytoplasm.…”

Section: Discussionmentioning

confidence: 57%

Epithelial lineages of the small intestine have unique patterns of GATA expression

Dusing

Wiginton

2005

J Mol Hist

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The ability of the GATA family of factors to interact with numerous other factors, co-factors, and repressors suggests that they may play key roles in tissues and cells where they are expressed. Adult mouse small intestine has been shown to express GATA-4, GATA-5, and GATA-6, where they have been implicated in the activation of a number of intestinal genes. Determination of which GATA factor(s) are involved in a specific function in tissues expressing multiple family members has proven difficult. The immunohistochemical analysis presented here demonstrate that within the mouse small intestine GATA-4/-5/-6 are found to be uniquely distributed among the various differentiated lineages of the intestinal epithelium. Among differentiated cells GATA-4 is found only in the villous enterocytes. GATA-5 is absent from enterocytes, but was found in the remaining lineages: goblet, Paneth and enteroendocrine. Additionally, high levels of GATA-6 are found in only one of these differentiated cell types, the enteroendocrine lineage. The observed distribution suggests that the GATA factors may have distinct roles in lineage allocation, lineage maintenance, and/or terminal differentiation events in small intestine.

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Transcription Factor GATA-6 Is Expressed in Malignant Endoderm of Pediatric Yolk Sac Tumors and in Teratomas

Cited by 19 publications

References 32 publications

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

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

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

Epithelial lineages of the small intestine have unique patterns of GATA expression

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