Source:http://linkedlifedata.com/resource/pubmed/id/11691824
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
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| pubmed:dateCreated |
2001-11-5
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| pubmed:abstractText |
Carbonic anhydrase-9 (CA9), a transmembrane enzyme with an extracellular active site, is involved in the reversible metabolism of the carbon dioxide to carbonic acid. Up-regulation of CA by hypoxia and the hypoxia-inducible factor (HIF) pathway has been recently postulated (Wykoff et al. Cancer Res., 60: 7075-7083, 2000). In the present study we examined the expression of this enzyme in non-small cell lung cancer. Of 107 cases analyzed, 39 (36.4%) had strong membrane/cytoplasmic expression of CA9 and were grouped as positive. The staining was confined around areas of necrosis, and a significant association of CA9 expression with the extent of necrosis was noted (P = 0.004). Nevertheless, 38 of 74 cases with focal or extensive necrosis did not express CA9. CA9 expression was more frequent in the squamous cell histology (P = 0.001) and with advanced T stage (P = 0.009). A significant coexpression of CA9 with platelet-derived endothelial cell growth factor and basic fibroblast growth factor receptor expression was noted. Double staining of CA9 with anti-CD31 monoclonal antibody revealed an overall higher microvessel density in the areas expressing CA9 than in negative areas (P = 0.0005). Thirty-one of 38 CA9-positive cases were positive for HIF1a/HIF2a, but HIF positivity was a more common event (68 of 107) and their patterns of expression were diffuse (not confined in the necrotic areas). A direct association of CA9 expression with epidermal growth factor receptor, c-erbB-2, and MUC1 expression was also noted (P < 0.04). Survival analysis showed that CA9 expression is related to poor prognosis. CA9 expression in tumors with low vascularization defined a prognosis similar to the one of patients with highly angiogenic tumors. Multivariate analysis revealed that CA9 expression is a significant prognostic factor independent of angiogenesis. We conclude that CA9 is an important molecule in non-small cell lung cancer, the up-regulation of which occurs in highly hypoxic/necrotic regions of the tumors. The expression of CA9 is linked to the expression of a constellation of proteins involved in angiogenesis, apoptosis inhibition, and cell-cell adhesion disruption, which explains the strong association of CA9 with poor outcome.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/CA9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carbonic Anhydrases,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Mucin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Epidermal Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine Phosphorylase,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/endothelial PAS domain-containing...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0008-5472
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
1
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| pubmed:volume |
61
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7992-8
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11691824-Adenocarcinoma,
pubmed-meshheading:11691824-Adult,
pubmed-meshheading:11691824-Aged,
pubmed-meshheading:11691824-Antigens, Neoplasm,
pubmed-meshheading:11691824-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:11691824-Carbonic Anhydrases,
pubmed-meshheading:11691824-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:11691824-Carcinoma, Squamous Cell,
pubmed-meshheading:11691824-Cell Hypoxia,
pubmed-meshheading:11691824-Enzyme Induction,
pubmed-meshheading:11691824-Female,
pubmed-meshheading:11691824-Fibroblast Growth Factor 2,
pubmed-meshheading:11691824-Humans,
pubmed-meshheading:11691824-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11691824-Lung Neoplasms,
pubmed-meshheading:11691824-Male,
pubmed-meshheading:11691824-Middle Aged,
pubmed-meshheading:11691824-Mucin-1,
pubmed-meshheading:11691824-Necrosis,
pubmed-meshheading:11691824-Neoplasm Proteins,
pubmed-meshheading:11691824-Neovascularization, Pathologic,
pubmed-meshheading:11691824-Prognosis,
pubmed-meshheading:11691824-Receptor, Epidermal Growth Factor,
pubmed-meshheading:11691824-Receptor, erbB-2,
pubmed-meshheading:11691824-Signal Transduction,
pubmed-meshheading:11691824-Thymidine Phosphorylase,
pubmed-meshheading:11691824-Trans-Activators,
pubmed-meshheading:11691824-Transcription Factors
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| pubmed:year |
2001
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| pubmed:articleTitle |
Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenic pathways and independently to poor outcome in non-small cell lung cancer.
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| pubmed:affiliation |
Tumour and Angiogenesis Research Group, Department of Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis 68100, Greece. targ@her.forthnet.gr
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| pubmed:publicationType |
Journal Article
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