충북대학교 종양연구소에서 다음과 같이 초청세미나를 개최하오니 많은 참여 부탁드립니다.
- 다 음 -
1. 연 자 : 이 한 웅 교수 (연세대학교)
2. 일 시 : 2018년 06월 14일 (목) 오후 4시
3. 연 제 : Function of a Novel p53 Target Gene in Cancer and Embryogenesis.
4. 장 소 : 종양연구소 세미나실 104호
5. 발 표 내 용
Retionoblastoma (Rb) is one of the most important genes in cell cycle regulation and tumorigenesis. To uncover the effect of Rb-deficiency, we analyzed the gene expression pattern of Rb-deficient Mouse embryonic fibroblasts (MEFs) using cDNA microarray. We identified a novel gene that was upregulated in Rb-deficient MEFs. This gene was named as Pierce1 (p53-induced expression 1 in Rb deficient cells) that has a N-terminal putative PEST signal in mice, which does not exist in human homologue. Pierce1 is highly expressed in brain, lung, kidney and testis in adult mice and humans.
We found that Pierce1 is a direct transcriptional target of p53 by using chromatin-immunoprecipitation assay and reporter assay in wildtype and p53-deficient MEF. However, Pierce1-deficient mice exhibited much less tumor nodules in DEN-induced carcinogenesis and K-Ras-LA2 lung cancer animal models. This anti-tumorigenic effect of Pierce1 deficiency appears to be mediated by NF-KB signaling.
Interestingly, Pierce1-null mice exhibited severe laterality defects, including situs inversus totalis and heterotaxy with randomized situs and left and right isomerisms. The spectrum of laterality defects was closely correlated with randomized expression of Nodal and its downstream genes, Lefty1/2 and Pitx2. The phenotype of Pierce1-null mice most closely resembled that of mutant mice with impaired ciliogenesis and/or ciliary motility of the node.
It would be interesting to further study the relationship between tumorigenesis and left-right symmetry specification