Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1002561 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25532311_1.fastq.gz | Fastqsanger.gz | |||
| SRR25532311_2.fastq.gz | Fastqsanger.gz | |||
| SRR25532312_1.fastq.gz | Fastqsanger.gz | |||
| SRR25532312_2.fastq.gz | Fastqsanger.gz | |||
| SRR25532313_1.fastq.gz | Fastqsanger.gz |
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Project description:TIMP-2 is an endogenous angiogenesis inhibitor, i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis. We overexpressed TIMP-2 and its mutant (does not inhibit MMP) in A549 human lung cancer cells and determined TIMP-2 and Ala+TIMP-2 transcriptional profiles, groups of genes and associated biological functions. We then injected the cells in NOD-SCID mice and RNA from tumors were isolated for further analysis to identify genes that are associated with tumor growth inhibition.
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Project description:KSHV is a principal causative agent of primary effusion lymphoma (PEL). Despite this knowledge about the close relationship between HGF/c-MET network and solid tumors development, the role of HGF/c-MET in KSHV-related malignancies remains mostly unclear. We report that HGF/c-MET pathway is highly active within KSHV+ PEL cells and plays important role in tumor cell survival/growth. Targeting HGF/c-MET by a selective inhibitor, PF-2341066, significantly induces PEL apoptosis through a complex of underlying mechanisms, including cell-cycle arrest and DNA damage. By using microarray analysis, we have identified the global gene profile controlled by HGF/c-MET pathway within KSHV+ PEL cell-lines and several novel âdruggableâ candidates closely related to cancer cell survival/growth. Finally, we found that targeting HGF/c-MET pathway by PF-2341066 effectively prevents PEL tumor expansion and/or reduce established lymphoma progression in vivo. PEL cells were treated with vehicle control or c-MET inhibitor PF-2341066 (0.8 µM) for 24 h, and the gene expression signature was compared to respective vehicle controls
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