Sex Steroid-Dependent and -Independent Angiogenesis in Uterine Endometrial Cancers

Summary

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, tumor-dormancy therapy against angiogenic potential in uterine endometrial cancers must be thoroughly considered. Upstream of the 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, as is basic fibroblast growth factor (bFGF) in cases of advanced and poorly differentiated uterine endometrial cancers. A transcriptional factor for angiogenesis, namely 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, may be an effective strategy to suppress uterine endometrial cancers as a novel tumor-dormancy therapy.