Overexpression of hypoxia-inducible factor-1 alpha in gastric adenocarcinoma.
BACKGROUND
The transcriptional factor hypoxia-inducible factor 1alpha (HIF-1alpha) controls angiogenesis and metabolism by upregulating hypoxia-induced genes, such as the vascular endothelial growth factor (VEGF) gene and the glucose transporter (GLUT-1) gene. In addition to its regulation by oncogenes or tumor suppressor genes such as HER2, p53, VHL, and PTEN, overexpression of HIF-1alpha is induced by hypoxia. Increased HIF-1alpha expression is associated with malignant potential, and with patient prognosis and response to chemoradiotherapy in some cancer types.


METHODS
We investigated the association between HIF-1alpha expression and clinicopathological characteristics, including the expression of VEGF and p53 proteins, in gastric cancer. Furthermore, we analyzed the impact of HIF-1alpha, VEGF, and p53 protein expression on resistance to chemotherapy in advanced gastric cancer.


RESULTS
Among 146 specimens from patients with gastric adenocarcinoma, 89 (61.0%), 52 (35.6%), and 102 (69.9%) were positive for HIF-1alpha, p53, and VEGF expression, respectively. The increased expression of HIF-1alpha protein correlated significantly with the increased expression of p53 (P < 0.0001) and VEGF (P = 0.0007). However, overexpression of these proteins was not associated with prognosis or clinicopathological status, with the exception of infrequent distant metastases. Furthermore, overexpression of these proteins was not associated with chemosensitivity in these patients with gastric cancer.


CONCLUSIONS
Our results indicate that overexpression of HIF-1alpha correlates significantly with p53 and VEGF protein expression in patients with gastric cancer; however, this overexpression shows no association with clinicopathological status, patient prognosis, or chemosensitivity.
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka (E-2), Suita, Osaka, 565-0871, Japan.
Naomi
N
Urano
Yoshiyuki
Y
Fujiwara
Yuichirou
Y
Doki
Masaki
M
Tsujie
Hirofumi
H
Yamamoto
Hiroshi
H
Miyata
Shuji
S
Takiguchi
Takushi
T
Yasuda
Masahiko
M
Yano
Morito
M
Monden
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D002454:Cell Differentiation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016159:Tumor Suppressor Protein p53; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A