Chemical genomic studies of small molecule modulator of Wnt/β-catenin pathway = Wnt/β -catenin pathway의 저분자 화합물 조절인자에 관한 화학유전체학적 연구

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Despite of the enormous knowledge accumulated about the genetic basis of human cancer, there have been only a few drugs which target the genetic differences between tumor cells and all normal cells in the body. To identify cancer-specific small molecules, a cell-based assay system which used co-culture strategy was newly developed. Co-culture of normal cells (WI38) and tumor cells (HCT-116) which expressed two different fluorescent proteins (YFP and CFP, respectively) allowed facile screening for cancer-specificity. Among 20,000 compounds screened, a novel compound, CGK3237, was identified that inhibited specifically the growth of HCT-116. Surprisingly, it was found out that only the growth of a certain type of cancer cells which had deregulated Wnt signaling pathway was selectively affected by CGK3237. By using a reporter assay for Wnt-dependent transcriptional activation, it was demonstrated that CGK3237 down-regulated the mRNA level of β -catenin and inhibited the occupancy of β-catenin onto TCF/LEF-responsive element. Consistent with this result, the activity of constitutively activated β-catenin in SW480 cells was also disturbed by CGK3237. The exact cellular target of CGK3237 was not identified yet, but these results suggest that chemical genomic approach is a very powerful method in searching for a novel anti-cancer drug.
Advisors
Kim, Tae-Kookresearcher김태국researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2005
Identifier
243528/325007  / 020023524
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 2005.2, [ iv, 42 p. ]

Keywords

Sialyltransferase; Galactosyltransferase; Wnt/β-catenin pathwayosylation; Chemical Genomics; DEAE Chromatographyv 2-D HPLCnjugation; DEAE 크로마토그래피; 시알산 전이효소; 갈락토오스 전이효소; Wnt/β-catenin 경로; 화학유전체학

URI
http://hdl.handle.net/10203/28054
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=243528&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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