Gene expression analysis in human breast cancer associated blood vessels.
dc.contributor.author | Jones, DT | en |
dc.contributor.author | Lechertier, T | en |
dc.contributor.author | Mitter, R | en |
dc.contributor.author | Herbert, JMJ | en |
dc.contributor.author | Bicknell, R | en |
dc.contributor.author | Jones, JL | en |
dc.contributor.author | Li, J-L | en |
dc.contributor.author | Buffa, F | en |
dc.contributor.author | Harris, AL | en |
dc.contributor.author | Hodivala-Dilke, K | en |
dc.date.accessioned | 2017-11-27T15:34:37Z | |
dc.date.available | 2017-11-27T15:34:37Z | |
dc.date.issued | 2012 | en |
dc.identifier.uri | http://hdl.handle.net/10026.1/10293 | |
dc.description.abstract |
Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold) in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC) of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of potentially novel anti-angiogenic targets that are likley to be, but not exclusivley, relevant to breast cancer. | en |
dc.format.extent | e44294 - ? | en |
dc.language | eng | en |
dc.language.iso | eng | en |
dc.subject | Angiogenesis Inhibitors | en |
dc.subject | Animals | en |
dc.subject | Antibodies | en |
dc.subject | Antibodies, Monoclonal, Humanized | en |
dc.subject | Aorta, Thoracic | en |
dc.subject | Bevacizumab | en |
dc.subject | Breast Neoplasms | en |
dc.subject | Carcinoma, Ductal, Breast | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Female | en |
dc.subject | Gene Expression Profiling | en |
dc.subject | Humans | en |
dc.subject | Immunohistochemistry | en |
dc.subject | In Vitro Techniques | en |
dc.subject | Mice | en |
dc.subject | Mice, Inbred BALB C | en |
dc.subject | Mice, Inbred C57BL | en |
dc.subject | Mice, SCID | en |
dc.subject | Microscopy, Confocal | en |
dc.subject | Neoplasms, Experimental | en |
dc.subject | Neovascularization, Pathologic | en |
dc.subject | Oligonucleotide Array Sequence Analysis | en |
dc.subject | Platelet Endothelial Cell Adhesion Molecule-1 | en |
dc.subject | RNA Interference | en |
dc.subject | Transplantation, Heterologous | en |
dc.subject | Tumor Burden | en |
dc.subject | Vascular Endothelial Growth Factor A | en |
dc.title | Gene expression analysis in human breast cancer associated blood vessels. | en |
dc.type | Journal Article | |
plymouth.author-url | https://www.ncbi.nlm.nih.gov/pubmed/23056178 | en |
plymouth.issue | 10 | en |
plymouth.volume | 7 | en |
plymouth.publication-status | Published | en |
plymouth.journal | PLoS One | en |
dc.identifier.doi | 10.1371/journal.pone.0044294 | en |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine | |
dc.publisher.place | United States | en |
dcterms.dateAccepted | 2012-08-01 | en |
dc.identifier.eissn | 1932-6203 | en |
dc.rights.embargoperiod | Not known | en |
rioxxterms.versionofrecord | 10.1371/journal.pone.0044294 | en |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | en |
rioxxterms.licenseref.startdate | 2012 | en |
rioxxterms.type | Journal Article/Review | en |