Sex steroid-dependent angiogenesis in uterine endometrial cancers.
In general, tumors induce angiogenic factors specific to them, which leads to angiogenesis with advancement. However, angiogenesis in uterine endometrial cancers is complicated because hormone dependency in growth also modifies the angiogenic potential. Therefore, anti-angiogenic therapy for tumor dormancy in uterine endometrial cancers must be thoroughly considered. The upstream of vascular endothelial growth factor (VEGF) gene conserves estrogen-responsive elements. Progesterone primed with estrogen induces thymidine phosphorylase (TP) in uterine endometrium. Sex steroid-dependent VEGF and TP are highly expressed in cases of early stage and well-differentiated uterine endometrial cancers, and basic fibroblast growth factor (bFGF) in cases of advanced and poorly differentiated uterine endometrial cancers. A transcriptional factor for angiogenesis, ETS-1, is linked to VEGF in well-differentiated uterine endometrial cancers, and to bFGF in poorly differentiated uterine endometrial cancers. Therefore, even if dedifferentiation and angiogenic switching occur due to advancement and long-term hormone therapy, the inhibition of ETS-1 along with main angiogenic factors might be an effective strategy to suppress uterine endometrial cancers as a novel anti-angiogenic therapy.
Fujimoto
Jiro
J
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan. jf@cc.gifu-u.ac.jp
Toyoki
Hiroshi
H
Jahan
Israt
I
Alam
Syed Mahfuzul
SM
Sakaguchi
Hideki
H
Sato
Eriko
E
Tamaya
Teruhiko
T
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000098:blood supply* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
D020533:Angiogenesis Inhibitors; C494041:ETS1 protein, human; D012739:Gonadal Steroid Hormones; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013939:Thymidine Phosphorylase