Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-12-12
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0165-4608
pubmed:author
pubmed:issnType
Print
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
168-72
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Mutation analysis of the HIF-1alpha oxygen-dependent degradation domain in invasive breast cancer.
pubmed:affiliation
Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't