PMID- 16337862
OWN - NLM
STAT- MEDLINE
DCOM- 20060131
LR  - 20131121
IS  - 0165-4608 (Print)
IS  - 0165-4608 (Linking)
VI  - 163
IP  - 2
DP  - 2005 Dec
TI  - Mutation analysis of the HIF-1alpha oxygen-dependent degradation domain in 
      invasive breast cancer.
PG  - 168-72
AB  - 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.
FAU - Vleugel, Marije M
AU  - Vleugel MM
AD  - Department of Pathology, University Medical Center Utrecht, PO Box 85500, 3508 GA 
      Utrecht, The Netherlands.
FAU - Greijer, Astrid E
AU  - Greijer AE
FAU - van der Wall, Elsken
AU  - van der Wall E
FAU - van Diest, Paul J
AU  - van Diest PJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Genet Cytogenet
JT  - Cancer genetics and cytogenetics
JID - 7909240
RN  - 0 (DNA Primers)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Base Sequence
MH  - Breast Neoplasms/*genetics/*pathology
MH  - DNA Primers
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Immunohistochemistry
MH  - *Mutation
MH  - *Neoplasm Invasiveness
MH  - Oxygen/*metabolism
MH  - Polymerase Chain Reaction
EDAT- 2005/12/13 09:00
MHDA- 2006/02/01 09:00
CRDT- 2005/12/13 09:00
PHST- 2004/12/28 00:00 [received]
PHST- 2005/05/13 00:00 [revised]
PHST- 2005/05/16 00:00 [accepted]
PHST- 2005/12/13 09:00 [pubmed]
PHST- 2006/02/01 09:00 [medline]
PHST- 2005/12/13 09:00 [entrez]
AID - S0165-4608(05)00275-X [pii]
AID - 10.1016/j.cancergencyto.2005.05.008 [doi]
PST - ppublish
SO  - Cancer Genet Cytogenet. 2005 Dec;163(2):168-72. doi: 
      10.1016/j.cancergencyto.2005.05.008.