Growth and Differentiation Factor 3 Is Transcriptionally Regulated by OCT4 in Human Embryonic Carcinoma Cells.
Growth and differentiation factor 3 (GDF3), a mammalian-specific transforming growth factor β ligand, and OCT4, one of key stem cell transcription factors, are expressed in testicular germ cell tumors (TGCTs) as well as pluripotent stem cells. To understand the molecular mechanism by which OCT4 and GDF3 function in tumorigenesis as well as stemness, we investigated the transcriptional regulation of GDF3 mediated by OCT4 in human embryonic carcinoma (EC) NCCIT cells, which are pluripotent stem cells of TGCTs. GDF3 and OCT4 was highly expressed in undifferentiated NCCIT cells and then significantly decreased upon retinoic acid-induced differentiation in a time-dependent manner. Moreover, GDF3 expression was reduced by short hairpin RNA-mediated knockdown of OCT4 and increased by OCT4 overexpression, suggesting that GDF3 and OCT4 have a functional relationship in pluripotent stem cells. A promoter-reporter assay revealed that the GDF3 promoter (-1721-Luc) activity was significantly activated by OCT4 in a dose-dependent manner. Moreover, the minimal promoter (-183-Luc) was sufficient for OCT4-mediated transcriptional activation and provided a potential binding site for the direct interaction with OCT4. Collectively, this study provides the evidence about the regulatory mechanism of GDF3 mediated by OCT4 in pluripotent EC cells.
Department of Biomedical Science, College of Life Science, CHA University.
Mi-Hee
MH
Han
Sung-Won
SW
Park
Hyun-Jin
HJ
Do
Hak-Jae
HJ
Chung
Hyuk
H
Song
Jin-Hoi
JH
Kim
Nam-Hyung
NH
Kim
Keun-Hong
KH
Park
Jae-Hwan
JH
Kim
D018236:Carcinoma, Embryonal / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055451:Growth Differentiation Factor 3 / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic
D055451:Growth Differentiation Factor 3; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human