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Growth and Differentiation Factor 3 Is Transcriptionally Regulated by OCT4 in Human Embryonic Carcinoma Cells

Mi-Hee Han, Sung-Won Park, Hyun-Jin Do, Hak-Jae Chung, Hyuk Song, Jin-Hoi Kim, Nam-Hyung Kim, Keun-Hong Park, Jae-Hwan Kim

Biol Pharm Bull. 2016;39(11):1802-1808.

PMID: 27803451

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413736 GDF-3 human GDF-3 human Price
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