BNIP3 expression is linked with hypoxia-regulated protein expression and with poor prognosis in non-small cell lung cancer.
BNIP3 is a proapoptotic protein regulated by hypoxia-inducible factor 1. We analyzed BNIP3 expression in 105 tumor samples from early operable, non-small lung cancer and the relationship of expression to hypoxia-inducible factor 1alpha, other hypoxia-regulated pathways, and prognosis. There was strong cytoplasmic expression in >10% of cells in 40 of 105 cases. BNIP3 expression was associated significantly with high hypoxia-inducible factor 1alpha (P = 0.003), carbonic anhydrase 9 (P = 0.04), and was inversely associated with bcl-2 expression (P = 0.009). High BNIP3 expression was a major independent factor for overall survival. Thus, high expression of a hypoxia regulated proapoptotic pathway was associated with a selection of an aggressive phenotype in vivo.
Departments of Pathology and Radiotherapy/Oncology, Democritus University of Thrace, Alexandroupolis, Greece. targ@her.forthnet.gr
Alexandra
A
Giatromanolaki
Michael I
MI
Koukourakis
Heidi M
HM
Sowter
Efthimios
E
Sivridis
Spencer
S
Gibson
Kevin C
KC
Gatter
Adrian L
AL
Harris
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
C090121:BNIP3 protein, human; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors