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Hum. Reprod. Advance Access published online on August 27, 2004
Human Reproduction, doi:10.1093/humrep/deh424
© 2004 by European Society of Human Reproduction and Embryology
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Received December 16, 2003
Revised June 2, 2004
Accepted June 24, 2004

Article

Roles of p38 and c-jun in the differentiation, proliferation and immortalization of normal human endometrial cells

In-Sun Hong 1, Seok-Hyun Kim 2, Mi Kyoung Koong 3, Jin Hyun Jun 3, Sung-Hoon Kim 4, Yong-Soon Lee 1*, Kyung-Sun Kang 1*

1 Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea
2 Laboratory of Reproductive Biology and Infertility, College of Medicine, Seoul National University, Seoul 151-742, Korea
3 Department of Biology and Infertility, Samsung Cheil Hospital and Women's Healthcare Center, Sungkyunkwan University School of Medicine, Seoul 100-380, Korea
4 Graduate School of East-West Medical Science, Kyunghee University, Yongin 449-701, Korea

* To whom correspondence should be addressed. E-mail: kangpub{at}snu.ac.kr or leeys@snu.ac.kr.


  Abstract

BACKGROUND: It has been reported that p38 and c-jun operate as mediators of cell proliferation and differentiation. Therefore, by studying the roles of c-jun and p38 in the proliferation and differentiation of normal human endometrial cells, we can better understand the mechanism of these processes in endometrial cells. METHODS: Separation of glandular and stromal components was based on a modification of the work of Satyaswaroop et al. To confirm the purification of the endometrial cells and the expression of the transfected SV40 large T antigen, immunocytochemical analysis and western blot analysis were performed. RESULTS: There were polygonal shapes in the stromal cells in the early passage 1-2, while the aged endometrial stromal cells were spindle shaped. To investigate passage-dependent molecular events in endometrial cells, the c-jun and pp38 levels were examined. Both c-jun and pp38 were significantly reduced with cellular aging and passages. To understand the role of c-jun, endometrial stromal cells were treated with SP600125 which is a specific inhibitor of c-jun. SP600125 induced morphological changes of young endometrial stromal cells with polygonal shape; the young cells appeared as aged endometrial cells with spindle shape. In addition, an immortalized endometrial cell line was established and shown to express activated c-jun, similiar to normal endometrial cells. CONCLUSIONS: These results suggest that the modulation of p38 and c-jun may play an important role in the differentiation and proliferation of human endometrial cells.

Keywords: c-jun; differentiation; endometrial epithelial cells; endometrial stromal cells; p38.
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