Dataset Information

Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD

ABSTRACT: The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds pollutants, therapeutic drugs and endogenous ligands. The AHR is expressed in all breast cancer subtypes and it can switch the aggressiveness of breast cancer cells from low to high depending on the ligand that it binds. Jagged 1 (JAG1) is a NOTCH receptor ligand that is overexpressed in basal-like breast cancer. JAG1 promotes breast cancer progression in part by increasing the migratory and invasive activity of breast cancer cells (BCCs). The regulation of JAG1 by AHR in MCF-7 and MDA-MB-231 BCCs by two AHR ligands (TCDD and ITE) was investigated in this report. TCDD is the prototype AHR ligand, and ITE is a non-toxic endogenous AHR ligand with anti-cancer activity. Ingenuity pathway analysis (IPA) revealed a significant association between TCDD-regulated genes (TRGs) and cell movement. Short interfering RNA (siRNA)-directed knockdown of AHR confirmed TCDD-stimulated decreases in JAG1 required AHR expression. TCDD-induced reductions in JAG1 were inhibited by the AHR antagonist CH-223191. The endogenous non-toxic AHR ligand ITE also reduced JAG1 by activating AHR in BCCs. MDA-MB-231 are basal-like BCCs that are highly migratory and invasive, and these cancer cell attributes were significantly inhibited by ITE. We reduced JAG1 with targeting siRNA, and the outcome mirrored ITE, it suppressed TNBC cell migration and invasive activity. Collectively, these findings are the first showing that ITE is a tumor-suppressing AHR ligand in TNBC cells in part because it reduces JAG1 expression

ORGANISM(S): Homo sapiens

PROVIDER: GSE98514 | GEO | 2018/08/15

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: JAG-1 is a ligand of Notch signaling and can regulate cell differentiation and proliferation in cancers. Recent studies indicated that JAG1 is a gene associated with cancer progression. Therefore, we investigated the role of JAG1 in lung cancer progression. Methods: The expression of JAG1 was manipulated by overexpression or RNA silencing in several human lung cell lines. The effect of JAG1 on tumorigenesis and invasion was assessed by the cell anchorage-independent growth, cell proliferation, cell migration and invasion assays in vitro as well as metastasis in vivo. The potential downstream genes of JAG1 were identified by oligonucleotide microarrays and quantitative reverse transcriptionÂ¡Vpolymerase chain reaction (RT-PCR). We further measured JAG1 expression in lung cancer specimens by RT-PCR. Correlation between JAG1 expression and overall survival of lung cancer patients was determined by using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided. Results: JAG1 enhanced anchorage-independent growth, cell migration, invasion in the lower invasive cells, CL1-0. JAG1 also increased the capability of migration and invasion in the other two lung cancer cell lines (A549 and NCI-H226). The silencing of JAG1 inhibited migration and invasion activities of the higher invasive cells, CL1-5, by siRNA technology. The invasion-promoting activity of JAG1 was also demonstrated in vivo by using a mouse metastasis model. By microarray analysis, we found that the expression of heat shock 70kDa protein 2 (HSPA2) was activated by JAG1 overexpression and eliminated by JAG1 silencing. Moreover, lung cancer patients with high JAG1 expressing tumors had shorter overall survival than those with low-expressing tumors. Conclusion: JAG1 might be an oncogene which promotes colonogenesis and metastasis, and high JAG1 expression is associated with shorten survival in lung cancer. In this investigation, we used a lung cancer invasion cell model to identify the genes involved in cancer progression. JAG1 is a potential oncogene whose expression is correlated to the survival of patients with breast, prostate and liver cancers. However, the role of JAG1 in lung caner progression has not been reported, particularly in metastasis. Here, JAG1 was ectopically expressed in lower invasive lung cancer cell line its impact on colonogenesis, migration and invasiveness was assessed. The underlying mechanism was explored by JAG1-expressed transfectants and microarrays and the clinical relevance was evaluated by quantitative RT-PCR.

Dataset Information

Expression profiling of four replicates of MCF-7 cells treated with 100nM TCDD

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets