체외 배양된 자궁내막세포에서의 DOC-1 유전자의 발현 조절
In Vitro Regulation of DOC-1 Gene Expression in Uterine Endometrial Cells
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초록
포배의 착상은 구조 및 기능적으로 준비된 자궁내막의 체계적 반응에 의하여 진행되는데 자궁 내막에서 엄격히 통제된 급격한 세포의 증식과 분화가 진행된다. 구강 상피세포암의 억제자로 알려진 Doc-1이 자궁에서 스테로이드 호르몬에 의하여 발현되며 세포 증식을 조절할 것으로 추정되어 왔으나 그 정확한 발현 변화에 대한 이해가 불충분하였다. 따라서 본 연구에서는 체외에서 탈락막 반응 모델 확립을 통하여 세포의 증식과 분화 진행과정에서 Doc-1의 발현 조절 기작을 알아보고자 하였다. 생쥐 자궁내막을 이용한 탈락막반응은 기질세포를 순수하게 분리하여 배양하면서 프로게스테론과 에스트로겐을 함유한 유도 배양액으로 유도하였다. 탈락막 유도 과정에서 배양 24 시간까지 세포의 증식이 유의하게 증가하였고 그 후에는 감소하였다. 한편 탈락막세포로의 분화는 분화유도 48시간에 거의 모든 세포에서 진행되었다. 또한 Doc-1 단백질의 발현이 분화유도 시간과 비례적으로 증가하였고 탈락막 세포에 위치하였다. 이러한 결과를 바탕으로 착상이 진행되는 자궁내막에서 Doc-1의 발현이 스테로이드 호르몬과 탈락막 분화와 연계되어 조절되고 Doc-1 단백질이 탈락막세포의 세포분열 억제를 유도하는 것을 제안할 수 있다.
Abstract
Implantation of blastocyst into the uterine endometrium is established by the existence of histologically and functionally prepared uterine endometrium. Doc-1, an oral cancer suppressor gene, is expressed under the control of steroid hormones and has been suggested as a proliferation regulator of endometrial cells. However, the role is not much clear and in this study we examined the expression modulation of Doc-1 in decidualizing cells in vitro. In vitro decidualization was performed in endometrial stroma cells using progesterone and estrogen. Until 24 hr after decidual induction the proliferation of stroma cell was significantly increased but decreased after then. On the other hand, most of the cells differentiated into decidual cell after 48 hr of induction. The Doc-1 protein was co-localized in a specific deciudal cells and colocalization rate was increased in a parallel manner with the induction time. Based on these results, it is suggested that Doc-1 expression is under the control of both steroid hormones and decidual signals, and Doc-1 protein is involved in suppression of the proliferation of decidualizing cells.
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