Plausible linkage of hypoxia-inducible factor (HIF) in uterine endometrial cancers.
OBJECTIVE
Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with the angiogenic transcription factor hypoxia-inducible factor (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine endometrial cancers.


METHODS
Sixty patients underwent curative resection for uterine endometrial cancers. In the tissue of 60 uterine endometrial cancers, HIF-1alpha, HIF-2alpha and HIF-1beta mRNA levels, and the ratio of angiopoietin (Ang)-2 to Ang-1 (Ang-2/Ang-1) mRNA levels were determined by RT real-time PCR; histochemical scores and localization of HIF-1alpha were determined by immunohistochemistry. Levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), thymidine phosphorylase (TP) and interleukin-8 (IL-8) were determined by enzyme immunoassay.


RESULTS
In stage I uterine endometrial cancers, HIF-1alpha histochemical scores and mRNA levels significantly increased with myometrial invasion of uterine endometrial cancers. HIF-1alpha histochemical scores and mRNA levels correlated with the levels of Ang-2/Ang-1 and IL-8.


CONCLUSIONS
The angiogenic mediator HIF-1alpha, linked to Angs and IL-8, might work on angiogenesis with myometrial invasion of cancer cells in uterine endometrial cancers.
Fujimoto
Jiro
J
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu City, Japan. jf@gifu-u.ac.jp
Sato
Eriko
E
Alam
Syed Mahfuzul
SM
Jahan
Israt
I
Toyoki
Hiroshi
H
Hong
Bao Li
BL
Sakaguchi
Hideki
H
Tamaya
Teruhiko
T
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016209:Interleukin-8; D012333:RNA, Messenger; D013939:Thymidine Phosphorylase; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000099162:Endothelial PAS Domain-Containing Protein 1; C497396:ARNT protein, human; C497442:HIF1A protein, human; C467484:VEGFA protein, human