No amplifications of hypoxia-inducible factor-1alpha gene in invasive breast cancer: a tissue microarray study.
OBJECTIVE
Hypoxia Inducible Factor-1 (HIF-1) is an important transcription factor that stimulates tumour growth and metastases via several pathways, including angiogenesis and altered metabolism. Activation of HIF-1 depends on the levels of its alpha-subunit, which increase during hypoxia. Recent studies showed that the HIF-1alpha gene was amplified in prostate cancer, leading to overexpression of HIF-1alpha at normoxia. The aim of this study was to evaluate the presence of HIF-1alpha gene amplifications in invasive breast cancer as an explanation for HIF-1alpha protein overexpression.


METHODS
Protein and gene expression of HIF-1alpha were analyzed on a tissue microarray of 94 breast cancers by immunohistochemistry and fluorescent in situ hybridization (FISH), respectively.


RESULTS
Overexpression of HIF-1alpha protein was found in 58/94 (62%) of patients. No amplifications of the HIF-1alpha gene were detected.


CONCLUSIONS
Increased protein levels of HIF-1alpha are not associated with amplification of the HIF-1alpha gene in human breast cancer. Therefore, other mechanisms than gene amplification must be responsible for HIF-alpha overexpression at normoxia.
Vleugel
Marije M
MM
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Bos
Reinhard
R
Buerger
Horst
H
van der Groep
Petra
P
Saramäki
Outi R
OR
Visakorpi
Tapio
T
van der Wall
Elsken
E
van Diest
Paul J
PJ
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D040081:Protein Array Analysis / Q000379:methods*; D014157:Transcription Factors / Q000235:genetics*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D010100:Oxygen