@entity5 cells often appear in a deviant differentiated stage, and dedifferentiation is a hallmark of @entity5 ; however, the causative mechanism of the global changes in dedifferentiation is not understood. The GATA transcription factors function in cell lineage specification during embryonic development and organ formation. The transcriptional targets of the GATA factors in early embryonic development include Disabled-2 and collagen IV, markers for epithelial lineages. @entity28430 and @entity70457 are expressed strongly and are localized in the nucleus in ovarian surface epithelial cells in tissues or primary cell cultures. By immunohistochemistry, we found that 82% of the 50 @entity5 analyzed had lost @entity70457 function, either by a complete absence of expression or by cytoplasmic mislocalization. The frequent loss of @entity70457 was also confirmed in a panel of ovarian surface epithelial and @entity5 cell lines. Although @entity28430 is absent only in a small percentage (14%) of @entity43 , it is lost in the majority of established cell lines in culture. The loss of @entity70457 correlates with the loss of Disabled-2, collagen IV, and laminin, markers for epithelial cell types. Loss of GATA factors was also found in an in vitro model for spontaneous transformation of @entity35 ovarian epithelial cells. Repression of @entity70457 by small interfering (si)RNA approach in cultured cells leads to dedifferentiation as indicated by the loss of Disabled-2 and laminin expression. Restoration of GATA factors expression by ectopic transfection suppresses cell growth and is incompatible with the maintenance of the cells in culture. However, restoration of @entity28430 and @entity70457 expression is not able to induce expression of endogenous Disabled-2 in @entity5 cells, suggesting that the loss of GATA factors and dedifferentiation are irreversible processes. In conclusion, we observed the inappropriate expression and cellular localization of the GATA transcription factors in @entity43 tissues and @entity5 cell lines, and we have demonstrated that down-regulation of GATA factor expression leads to dedifferentiation. We propose that alterations of GATA transcription factor expression and aberrant nucleocytoplasmic localization may contribute to the anomalous epithelial dedifferentiation of the @entity43 cells.

Anomalous expression of epithelial differentiation-determining GATA factors in XXXX .

@entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian tumors', 'ovarian tumor'] @entity28430 :: ('54254(Tax:10116)', 'Gene') :: ['GATA-4'] @entity70457 :: ('29300(Tax:10116)', 'Gene') :: ['GATA-6'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'Tumor', 'malignancy', 'tumors'] @entity35 :: ('10116', 'Species') :: ['rat']
@entity43 :: (MESH:D010051,Disease) :: ['ovarian tumorigenesis']
