자궁내막증에서 Cyclins-CDKs와 CDKIs에 의한세포주기 조절경로에 관한 연구
Cell Cycle Signaling Pathway by Cyclins-CDKsand CDKIs in Endometriosis
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목적 : 본 연구는 자궁내막증과 연관된 cyclin-cyclin dependent kinase (CDK), cyclin dependent kinase inhibitor (CDKI)에 의한 세포주기 조절경로의 이상에 관하여 알아보고자 하였다. 연구 방법 : 자궁내막증 환자 38명에서 월경주기 중 난포기에 복강경 수술 및 소파술을 시행하여 난소에 발생한 자궁내막종 조직과 정상 조직 및 자궁내막 조직을 채취하였다. 각각으로부터 세포주기의 각 단계에 특이적인 cyclin D1, cyclin E 등의 핵단백질과 그들의 활성도에 직접적으로 기여하는 CDK molecule, CDKI인 p27kip1, p21 등의 발현도를 역전사 중합효소 연쇄반응 (reverse transcription-polymerase chain reaction, RT-PCR)과 Western blot analysis를 통해 전사 단계 (transcriptional level)와 번역 단계 (translational level)에서 각각 정량하였다. 결과 : 채취한 자궁내막종 조직과 정상 조직 및 자궁내막 조직으로 RT-PCR을 수행하여 cyclin D1, cyclin E와 그에 각각 작용하는 CDK molecule, p27kip1, p21의 mRNA 발현양상을 정량한 실험 결과, 정상 난소 조직에서보다 자궁내막종과 자궁내막 조직에서 cyclin D1-CDK6, cyclin E-CDK2의 발현이 유의하게 증가하였고 p27kip1의 발현은 유의하게 감소하였으나 자궁내막종 조직과 자궁내막 조직에서의 발현양상은 유의한 차이가 없었다. 한편 Western blot analysis에 의하면 마찬가지로 정상 난소 조직에서보다 자궁내막종과 자궁내막 조직에서 cyclin D1-CDK6, cyclin E-CDK2의 발현이 유의하게 증가하였고 p27kip1의 발현은 유의하게 감소하였으며 특히 자궁내막종 조직에서의 p27kip1의 발현량 감소가 현저하여 자궁내막 조직에서보다도 유의하게 감소되었다. 결론 : 본 연구 결과에 따르면 세포주기 조절경로에서 번역 단계에서의 p27kip1이 자궁내막증과 밀접한 연관성이 있을 것으로 사료된다. 앞으로 자궁내막증과 관련된 세포주기 조절경로를 규명하기 위한 보다 많은 실험적 연구가 필요할 것이다.
Abstract
Objective : This study was undertaken to evaluate the cell cycle signaling pathway by cyclins-cyclin dependent kinases (CDKs) and cyclin dependent kinase inhibitors (CDKIs) in endometriosis. Methods : 38 women with endometriosis were recruited. Endometrioma and the normal ovarian tissues were obtained during laparoscopic surgery on the follicular phase of menstrual cycle. And then, the normal endometrial tissues were taken by currettage. Nuclear proteins (cyclin D1, cyclin E etc), CDK molecules and CDK inhibitors (p27kip1, p21 etc) were quantitated on transcriptional and translational levels by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Results : In RT-PCR analysis, the expression of cyclin D1-CDK6, cyclin E-CDK2 of endometrioma and eutopic endometrium was increased, and the expression of p27kip1 was decreased compared with normal ovary. The mRNA expression of cyclins-CDKs and p27kip1 was not significantly different between endometrioma and eutopic endometrium. In Western blot analysis, the expression of cyclin D1-CDK6, cyclin E-CDK2 was significantly increased and the expression of p27kip1 was significantly decreased in endometrioma and eutopic endometrium compared with normal ovary. And, the expression of p27kip1 in endometrioma was further decreased than that of eutopic endometrium. Conclusion : These results suggest that p27kip1 on the translational level, in the cell cycle signaling pathway, was closely related to endometriosis. In future, further experimental studies will be needed for the understanding of the cell cycle signaling pathway in endometriosis.
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