Dataset Information

Effect of 6-TG on apoptosis and cell cycle in MCF-7 breast cancer cells and its mechanisms through the regulation of DNMT1

ABSTRACT: Thioguanine (6-TG) as conventional drug has anti-tumor activity in various cancer cell lines. However, the effect of 6-TG on luminal subtypes breast cancer (ER+, PR+) is elusive. In this study, effect of 6-TG on MCF-7 breast cancer cell line (ER+, PR+) and its mechanisms were investigated. MCF-7 cells were treated with 6-TG and IC50 value was measured by cell counting kit-8 assay. DEGs were confirmed by RNA-seq. Apoptosis and cell cycle consequences were checked by flow cytometry and western blot. Our results showed that colony formation decreased obviously after 6-TG treatment. Moreover, with the treatment of 6-TG cell apoptosis percentage increased. DNMT1 mRNA and protein expression decreased and FAS expression increased in both expression level. Meanwhile, 6-TG treatment also induced MCF-7 cells to occur G2/M phase cell cycle arrest. Overall, our results indicated that 6-TG suppressed cell proliferation, induced G2/M phase arrest through DNMT1 mediated p53-dependent p21 signaling, and accelerated cell apoptosis through activated extrinsic apoptosis pathway which was caused by DNMT1 mediated FAS signaling.

ORGANISM(S): Homo sapiens

PROVIDER: GSE130161 | GEO | 2020/03/02

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:MCF-7:PF is a a new in vitro model of antihormone resistant breast cancer that exhibits the characteristics of acquired tamoxifen resistance in vivo. It is well known that estrogen (E2) induces apoptosis in long-term estrogen-deprived breast cancer cells, MCF-7:5C (PubMed References PMID:15862958, PMID:16333030). MCF-7:PF was derived from MCF-7:5C through inhibition of c-Src, which blocks E2-induced apoptosis, coverts E2 responses from apoptosis to proliferation. MCF-7:PF cell growth is stimulated by E2 and SERMS in an ERα-dependent manner. Abstract: A c-Src inhibitor blocks estrogen (E2)-induced stress and converts E2 responses from inducing apoptosis to stimulating growth in E2-deprived breast cancer cells. A resulting cell line, MCF-7:PF, is reprogrammed with features of functional estrogen receptor (ER) and over-expression of insulin-like growth factor-1 receptor beta (IGF-1Rβ). We addressed the question of whether the antiestrogenic selective ER modulator 4-hydroxytamoxifen (4-OHT) could target ER to prevent E2-stimulated growth in MCF-7:PF cells. Unexpectedly, 4-OHT stimulated cell growth in an ER-dependent manner. However, unlike E2, 4-OHT suppressed classic ER-target genes as does the pure antiestrogen ICI 182,780, even during growth stimulation. Chromatin-immunoprecipitation (ChIP) assay indicated that 4-OHT did not recruit ER or nuclear receptor coactivator 3 (SRC3) to the promoter of ER-target gene, pS2. Paradoxically, 4-OHT reduced total IGF-1Rβ but increased phosphorylation of IGF-1Rβ, which was responsible for the activation of the phosphatidylinositol-3 kinases (PI3K)/Akt signaling pathway. Mechanistic studies revealed that 4-OHT rapidly activated the non-genomic pathway through ER, but other membrane-associated proteins such as IGF-1Rβ and c-Src participated. Furthermore, 4-OHT was more potent than E2 to up-regulate membrane remodeling molecules and activated focal adhesion molecules to promote cell growth. Therefore, disruption of membrane-associated signaling completely abolished 4-OHT-stimulated cell growth, but not E2-stimulated cell growth. Despite continued suppression of classic ER-target genes, 4-OHT activated the complex network of cytoskeleton remodeling and extracellular matrix-related signaling which facilitated 4-OHT-stimulated cell growth. This study is the first to recapitulate a cellular model in vitro of acquired tamoxifen (TAM) resistance developed in athymic mice in vivo.

Dataset Information

Effect of 6-TG on apoptosis and cell cycle in MCF-7 breast cancer cells and its mechanisms through the regulation of DNMT1

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets