Decidualization is a biological and morphological process occurring in hES (human endometrial stromal) cells. Previously, we reported that PLD1 (phospholipase D1) plays an important role in cAMP-induced decidualization of hES cells. In the present study, we focused on how PLD1 expression is up-regulated during decidualization. Treatment with PKA (protein kinase A) inhibitors (Rp-cAMP or H89) or a Ras inhibitor (manumycin) partially inhibited PLD1 expression and decidua formation in response to cAMP treatment. Interestingly, dual inhibition of PKA and Ras completely inhibited PLD1 expression and cAMP-induced decidualization. These results suggest that PLD1 expression during decidualization is controlled additively by PKA and Ras. The use of inhibitors showed that extracellular-signal-regulated kinase, a downstream effector of Ras, was required for PLD activation and the morphological changes during decidualization, but not for the increase in PLD1 protein. Next, to investigate the regulator of the PLD1 gene at the transcriptional level, a promoter assay using deletion mutants of the PLD1 promoter was performed; the result indicated that PR (progesterone receptor) was a possible regulator of the PLD1 gene. In addition, chromatin immunoprecipitation assays on the PLD1 promoter identified PR as a transcription factor for PLD1 expression during 8-Br-cAMP-induced decidualization. Taken together, our findings demonstrate that PKA and Ras are novel regulators of PLD1 expression and also identify PR as a transcription factor for PLD1 expression during the decidualization of hES cells.
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Research Article|
April 27 2011
The progesterone receptor as a transcription factor regulates phospholipase D1 expression through independent activation of protein kinase A and Ras during 8-Br-cAMP-induced decidualization in human endometrial stromal cells
Ju Hwan Cho;
Ju Hwan Cho
1
*Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, Republic of Korea
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Mee-Sup Yoon;
Mee-Sup Yoon
1
*Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, Republic of Korea
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Jun Bon Koo;
Jun Bon Koo
*Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, Republic of Korea
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Yong Seok Kim;
Yong Seok Kim
*Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, Republic of Korea
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Ki-Sung Lee;
Ki-Sung Lee
†Department of Biology and Medicinal Science, College of Sciences and Technology, Pai Chai University, Daejeon 302-735, Republic of Korea
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Jung Han Lee;
Jung Han Lee
2
‡Department of Obstetrics and Gynecology, College of Medicine, Hanyang University, Guri Hospital, Guri City 471-701, Gyeonggi-Do, Republic of Korea
2Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Joong-Soo Han
Joong-Soo Han
2
*Biomedical Research Institute and Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul 133-791, Republic of Korea
2Correspondence may be addressed to either of these authors (email [email protected] or [email protected]).
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Publisher: Portland Press Ltd
Received:
October 04 2010
Revision Received:
January 19 2011
Accepted:
February 02 2011
Accepted Manuscript online:
February 02 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 436 (1): 181–191.
Article history
Received:
October 04 2010
Revision Received:
January 19 2011
Accepted:
February 02 2011
Accepted Manuscript online:
February 02 2011
Citation
Ju Hwan Cho, Mee-Sup Yoon, Jun Bon Koo, Yong Seok Kim, Ki-Sung Lee, Jung Han Lee, Joong-Soo Han; The progesterone receptor as a transcription factor regulates phospholipase D1 expression through independent activation of protein kinase A and Ras during 8-Br-cAMP-induced decidualization in human endometrial stromal cells. Biochem J 15 May 2011; 436 (1): 181–191. doi: https://doi.org/10.1042/BJ20101614
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