title: Wnt/Β-catenin and sex hormone signaling in endometrial homeostasis and cancer.
abstract: A delicate balance between estrogen and progestagen signaling underlies proper functioning of the female reproductive tract and, in particular, the monthly re- and degenerative phases characteristic of the menstrual cycle. Here, we propose that the canonical Wnt/β-catenin signaling pathway may underlie this finely tuned hormonal equilibrium in endometrial homeostasis and, upon its constitutive activation, lead to neoplastic transformation of the endometrium. During the menstrual cycle, estradiol will enhance Wnt/β-catenin signaling in the proliferative phase, while progesterone inhibits Wnt/β-catenin signaling, thus restraining estrogens' proliferative actions, during the secretory phase. In case of enhanced or unopposed estrogen signaling, constitutive activation of Wnt/β-catenin signaling will trigger endometrial hyperplasia, which may develop further into endometrial cancer.
authors.affiliation: Department of Obstetrics & Gynaecology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.|Departments of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics & Gynaecology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.|Departments of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Marten
authors.initials: M
authors.lastname: van der Zee
authors.affiliation: Departments of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Fodde
authors.affiliation: Department of Obstetrics & Gynaecology, Josephine Nefkens Institute, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Leen J
authors.initials: LJ
authors.lastname: Blok
mesh_terms: D000818:Animals; D018269:Carcinoma, Endometrioid / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D012739:Gonadal Steroid Hormones; D051153:Wnt Proteins; D051176:beta Catenin