In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. LB-156-LB-156
Abstract:
To explore if the Notch pathway were abnormally regulated during gastric tumorigenesis, abnormal DLL1 promoter methylation and inversely correlated mRNA expression were detected in cultured cell lines and patient samples. Elevated DLL1 expression was observed in gastric lesion like gastritis or erosion, but decreased DLL1 expression was detected in all four stages of gastric cancers (n = 44). To identify the effector genes and construct the possible Notch signaling network in gastric cancer, Myc-tagged Notch1 was overexpressed in gastric cancer cell line followed by the chromatin-immuno-precipitation sequencing (ChIP-seq) analysis. In ChIP-seq analysis, antibodies against Notch1, Rbpjκ, and Myc were used to identify the Notch1 targets while antibodies against trimethylated histone 3 at lysine 4 (H3K4me3) or lysine 27 (H3K27me3) were used to detect the associated epigenetic states. We found that the Notch1-overexpression suppressed the gastric tumoral growth, and the target loci-associated H3K4me3 (active chromatin) were reduced while the association with H3K27me3 (suppressive chromatin) were increased. Overall, the H3K4me3 and H3K27me3 combined bivalent marks were increased after Notch1-overexpression, and this was correlated with promoted stemness as indicated by the increased Oct4 and CD44 (reported gastric cancer stem cell like marker) expression. EZH2, a Polycomb protein, was found to be associated with Rbpjκ which further links the Notch signaling together with the maintenance of cell stemness. Therefore, Notch signaling might be critical for tumor formation in gastric cancer. (Supported by: NSC-102-2320-B-194-003-MY3 and NSC-102-2314-B-371-003-MY3, MOST Taiwan) Citation Format: Chia-Chen Chiu, Chien-Ju Lo, Chien-Heng Shen, Chung-Kuang Lu, Jian-Liang Chou, Pei-Yi Chu, Shu-Huei Hsiao, Min-Jen Tseng, Yu-Wei Leu, Chia-Chen Hsu. Increased Notch1 expression suppressed the growth but promoted the stemness of gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2015-LB-156
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-LB-156
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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