title: Gastrokine 1 induces senescence and apoptosis through regulating telomere length in gastric cancer.
abstract: The present study aims to investigate whether gastrokine 1 (GKN1) induces senescence and apoptosis in gastric cancer cells by regulating telomere length and telomerase activity. Telomere length, telomerase activity, and hTERT expression decreased significantly in AGSGKN1 and MKN1GKN1 cells. Both stable cell lines showed increased expression of TRF1 and reduced expression of the hTERT and c-myc proteins. In addition, TRF1 induced a considerable decrease in cell growth, telomerase activity, and expression of hTERT mRNA and protein. GKN1 completely counteracted the effects of c-myc on cell growth, telomere length, and telomerase activity. Interestingly, GKN1 directly bound to c-myc and down-regulated its expression as well as inhibited its binding to the TRF1 protein and a hTERT promoter. Furthermore, GKN1 triggered senescence, followed by apoptosis via up-regulating the p53, p21, p27, and p16 proteins and down-regulating Skp2. Telomere length in 35 gastric cancers was shortened significantly compared with the corresponding gastric mucosae, whereas GKN1 expression was inversely correlated with telomere length and c-myc and hTERT mRNA expression. Taken together, these results suggest that GKN1 may shorten telomeres by acting as a potential c-myc inhibitor that eventually leads to senescence and apoptosis in gastric cancer cells.
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of General Surgery, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Ho Seok
authors.initials: HS
authors.lastname: Seo
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Olga
authors.initials: O
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea. Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Suk Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea. Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Pathology, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea. Functional RNomics Research Center, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
authors.forename: Won Sang
authors.initials: WS
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D047369:Chromatin Immunoprecipitation; D006801:Humans; D036361:Peptide Hormones / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism / Q000648:ultrastructure*; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism
chemical_list: C477000:GKN1 protein, human; D036361:Peptide Hormones; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D035321:Telomeric Repeat Binding Protein 1; D019098:Telomerase