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GSE46564
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Anti-PDGF agents are routinely used as a key component in front-line therapy for the treatment of various cancers. However, molecular mechanisms underlying their impact on vascular remodeling in relation to the dose issue remain poorly understood. Here we show that in high PDGF-BB-producing tumors, anti-PDGF drugs significantly inhibited tumor growth and metastasis by preventing pericyte (PC) loss and vascular permeability. Surprisingly, the same anti-PDGF-BB drugs promoted tumor cell dissemination and metastasis in PDGF-BB-low-producing or negative tumors by ablating PCs from tumor vessels. At the molecular level, we show that the PDGFR- signaling pathway in PCs mediated the opposing effects and persistent exposure of PCs to PDGF-BB led to marked downregulation of PDGFR-. Inactivation of the PDGFR- signaling system led to decreased levels of integrin 11, resulted in impaired adhesion of PCs to collagen I, IV and laminin, two principal extracellular matrix components in blood vessels for interaction with these integrins. Our data suggest that tumor PDGF-BB levels may serve as an important biomarker for selection of tumor-bearing hosts for beneficial therapy and unsupervised practice of this group of drugs could potentially promote tumor invasion and metastasis.
Publication Title
Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Using microcell-mediated chromosome transfer (MMCT) into the mouse melanoma cell line, B16F10, we have previously found that human chromosome 5 carries a gene, or genes, that can negatively regulate TERT expression. To identify the gene responsible for the regulation of TERT transcription, we performed cDNA microarray analysis using parental B16F10 cells, telomerase negative B16F10 microcell hybrids with a human chromosome 5 (B16F10MH5), and its revertant clones (MH5R) with reactivated telomerase. Here we report the identification of PITX1, whose restoration leads to the downregulation of mouse tert (mtert) transcription, as a TERT suppressor gene. Additionally, both human TERT (hTERT) and mouse TERT (mtert) promoter activity can be suppressed by PITX1. We showed that three and one binding sites, respectively, within the hTERT and mtert promoters that express a unique conserved region are responsible for the transcriptional activation of TERT. Furthermore, we showed that PITX1 binds to the TERT promoter both in vitro and in vivo. Thus, PITX1 suppresses TERT transcription through direct binding to the TERT promoter, which ultimately regulates telomerase activity.
Publication Title
Identification of PITX1 as a TERT suppressor gene located on human chromosome 5.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hypoxia signature in Clear cell RCC
Publication Title
Regulation of endocytosis via the oxygen-sensing pathway.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples