Source:http://linkedlifedata.com/resource/pubmed/id/16337862
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2005-12-12
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pubmed:abstractText |
Hypoxia inducible factor-1 (HIF-1) is an important transcription factor that stimulates tumor growth and metastases via several pathways. Activation of HIF-1 depends on the presence of its alpha-subunit. Hypoxia increases HIF-1alpha levels by inhibiting prolyl-hydroxylase--mediated hydroxylation and thereby preventing proteosome degradation. Various other mechanisms might also contribute to HIF-1alpha expression, such as mutation of the oxygen dependent degradation domain (ODD), which prevents binding of prolyl-hydroxylases. Therefore, the presence of ODD mutations was evaluated as a possible explanation for diffuse HIF-1alpha protein expression often seen in invasive breast cancer. From a group of 200 primary breast cancers, 24 strong diffusely HIF-1alpha-positive tumor samples were identified with HIF-1alpha immunohistochemistry. DNA from these tumors was extracted from microdissected paraffin material and, after nested polymerase chain reaction, sequence analysis was performed to detect hif-1alpha ODD mutations. Additionally, five perinecrotically HIF-1alpha-positive breast cancers were analyzed as controls. All 24 diffuse and perinecrotic HIF-1alpha-positive breast cancers showed wild-type DNA sequences in the ODD domain. No mutations seem to occur in the ODD of hif-1alpha in HIF-1alpha overexpressing invasive breast cancer, which rules ODD mutations out as a possible explanation for the diffuse HIF-1alpha expression pattern often seen in this cancer.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0165-4608
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
168-72
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16337862-Base Sequence,
pubmed-meshheading:16337862-Breast Neoplasms,
pubmed-meshheading:16337862-DNA Primers,
pubmed-meshheading:16337862-Female,
pubmed-meshheading:16337862-Humans,
pubmed-meshheading:16337862-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:16337862-Immunohistochemistry,
pubmed-meshheading:16337862-Mutation,
pubmed-meshheading:16337862-Neoplasm Invasiveness,
pubmed-meshheading:16337862-Oxygen,
pubmed-meshheading:16337862-Polymerase Chain Reaction
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pubmed:year |
2005
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pubmed:articleTitle |
Mutation analysis of the HIF-1alpha oxygen-dependent degradation domain in invasive breast cancer.
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pubmed:affiliation |
Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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