자궁내막암에서 세포주기 조절과 관련된 TRPC 채널의 발견
Detection of TRPC channels related to cell cycle regulation in endometrial cancer
- 주제(키워드) Endometrial cancer , Cell cycle , TRPC channel
- 발행기관 아주대학교
- 지도교수 민철기
- 발행년도 2015
- 학위수여년월 2015. 2
- 학위명 석사
- 학과 및 전공 일반대학원 생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000018990
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Transient receptor potential (TRP) C channels are 〖Ca〗^(2+)-permeable non-selective cation channels, relaying a variety of stimuli to intracellular Ca2+ changes. 〖Ca〗^(2+) as a second messenger has diverse functions including control of gene expression, cell cycle, cell growth, cell death, and cell differentiation. Here, we aimed to ensure whether there is a relationship between TRPC channel expression and cell cycle progression in human endometrial cancer. Two non-selective TRPC channel blocker 2-APB and SKF-96365 hinder the cell proliferation as evidenced by MTT assay. The mRNAs of TRPC1 and TRPC6 were detected in human endometrial cancer AN3CA and KLE cells. To verify a relationship between TRPC channel expression and cell cycle progression, AN3CA cells was arrested at G1 phase and at G2/M phase through cell synchronization by utilizing mimosine and nocodazole, respectively, and concomitant expression level of TRPC1 and TRPC6 mRNAs were measured by RT-PCR. Results demonstrated the expression of TRPC1 and 6 channels were regulated in a cell cycle-dependent manner with the highest expression shown at G2/M phase. The TRPC6 channels were mainly localized to the cell membrane. In addition, G2/M phase arrest induced by non-specific TRPC channel blocker SKF-96365 led to apoptotic cell death. These results suggest that TRPC channels play an important role in regulation of cell cycle of endometrial cancer. The blocking of TRPC channels causes a cell cycle arrest and apoptotic cell death subsequently.
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CONTENTS
ABSTRACT 1
CONTENTS 3
INTRODUCTION 4
MATERIALS AND METHODS 9
RESULTS
TRPC channel subtype expression in endometrial cancer cells 10
AN3CA cell proliferation was inhibited by TRPC channel blockers 10
Cell cycle synchronization and cell-cycle dependent TRPC6 expression 11
Localization of TRPC6 channel in AN3CA cells at G2/M arrest 12
SK-96365 induced apoptotic cell death 12
DISCUSSION 15
REFERENCES 19
FIGURE LEGENDS 27
TABLE LEGENDS 31
국문 요약 32