Positive expression of HIF-2alpha/EPAS1 in invasive bladder cancer.
OBJECTIVE
To investigate the expression of hypoxia-inducible factor (HIF)-2alpha/endothelial PAS domain protein 1 (EPAS1) in bladder cancer.


METHODS
Two bladder cancer cell lines (T24, EJ-1) were examined for the expression of HIF-2alpha/EPAS1 mRNA by reverse transcriptase-polymerase chain reaction and HIF-2alpha/EPAS1 protein by Western blot analysis, respectively. Expression of HIF-2alpha/EPAS1 protein was also investigated immunohistochemically on paraffin-embedded sections from 24 patients with bladder cancer.


RESULTS
HIF-2alpha/EPAS1 mRNA and protein could be detected in the two bladder cell lines under normoxia. The normal urothelium and all 7 superficial cases (pTis-pTa) were negative for HIF-2alpha/EPAS1. Five of the 8 pT1 cases (62.5%) and all 9 muscle-invasive cases were positive. The invasive compartment showed stronger HIF-2alpha/EPAS1 immunoreactivity compared with the superficial compartment. All the tumor clusters infiltrating to the interstitial tissue among muscle fibers showed moderate to strong positive staining.


CONCLUSIONS
HIF-2alpha/EPAS1 is mostly expressed in invasive bladder cancer, which indicates a possible role for HIF-2alpha/EPAS1 in the invasion of bladder cancer.
Xia
Guangbin
G
Department of Urology and Reproductive Medicine, Graduate School Tokyo Medical and Dental University, Tokyo, Japan.
Kageyama
Yukio
Y
Hayashi
Tetsuo
T
Hyochi
Nobuhiko
N
Kawakami
Satoru
S
Kihara
Kazunori
K
D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins; D002295:Carcinoma, Transitional Cell / Q000737:chemistry*; D005260:Female; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000737:chemistry; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D000099162:Endothelial PAS Domain-Containing Protein 1