Krüppel-like transcription factor 6 transactivates pregnancy specific glycoprotein genes in trophoblast cells

RACCA ANA; CAMOLOTTO SOLEDAD; RENA VIVIANA; GENTI-RAIMONDI SUSANA; PANZETTA-DUTARI GRACIELA M

Los Cocos Argentina

Simposio; III Latin-American Symposium on Maternal-Fetal Interaction & Placenta: Basic and clinical research; 2007

Grupo Latinoamericano de investigación en Placenta

Human pregnancy-specific glycoproteins (PSGs) are encoded by 11 highly similar and transcriptionally active genes, essential for the maintenance of gestation. High levels of PSG biosynthesis are restricted to the placenta syncytiotrophoblast (STB), and only very low levels are found in other cell types, such as the choriocarcinoma Jeg3 cell line. PSGs are early biochemical markers of trophoblast differentiation. Krüppel-like factor- 6 (KLF6) plays a crucial role in the regulation of genes involved in differentiation, angiogenesis, cell cycle control and proliferation in several cell systems. Although it is highly expressed in human term placenta tissue, little is known about its role in regulating placenta specific genes. Objectives: In order to get further insight into PSG genes transcriptional regulation, we have investigated the roles of KLF6 and Small Nuclear RING Finger co-activator (SNURF) in trophoblast PSG expression. Methods: Western blot, immunofluorescence, transfection assays and qRT-PCR were used to explore the expression of these regulatory factors and their impact on PSG genes transcription. Results: KLF6 protein and transcript levels increase during in- vitro differentiation of cytotrophoblast isolated from third trimester placenta as well as in choriocarcinoma Jeg3 cell line. Overexpression of KLF6 increases trophoblastic PSG mRNA expression. PSG promoter constructs are activated by KLF6 and this effect is enhanced by the co-expression of the co-activator SNURF, which is expressed in trophoblastic cells. Conclusion: Our data provide evidence that KLF6 and SNURF may cooperate in regulating PSG-genes expression during trophoblast differentiation. Supported by CONICET, FONCyT and SECyT-UNC.