Up-regulation of hypoxia-inducible factor-1 alpha and VEGF mRNAs in peritoneal dissemination of patients with gastric cancer.
BACKGROUND
Gastric cancer often metastasizes to the peritoneal cavity in which tumor cells are exposed to hypoxia without systemic circulation. Hypoxia-inducible factor-1 (HIF-1) and its target gene, vascular endothelial growth factor (VEGF), may play a role in the development of peritoneal metastases.


METHODS
The mRNA levels of HIF-1 alpha and VEGF were examined in 21 normal gastric mucosa, 158 primary tumors and 18 peritoneal metastases by quantitative RT-PCR.


RESULTS
HIF-1 alpha and VEGF were significantly up-regulated in the peritoneal metastases compared with those of the normal mucosa and the primary tumors. A positive correlation between HIF-1 alpha and VEGF was observed in the peritoneal dissemination.


CONCLUSIONS
These results suggest that HIF-1 alpha and its target gene, VEGF, were up-regulated in the intraperitoneal tumors but not in the primary cancers of the stomach. Different microenvironments may influence the expressions of these genes.
Yoshikawa
Takaki
T
Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-Ku, Yokohama 241-0815, Japan.
Tsuburaya
Akira
A
Miyagi
Yohei
Y
Sekiguchi
Hironobu
H
Kimura
Masayuki
M
Cho
Haruhiko
H
Kobayashi
Osamu
O
D001483:Base Sequence; D017931:DNA Primers; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics*; D010534:Peritoneal Neoplasms / Q000235:genetics / Q000556:secondary*; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D017931:DNA Primers; D051793:Hypoxia-Inducible Factor 1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A