title: Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions.
abstract: Ovarian cancer (OC) is the most deadly gynaecological disease largely because the majority of patients are asymptomatic and diagnosed at later stages when cancer has spread to other vital organs. Therefore, the initial stages of this disease are poorly characterised. Women with BRCA1/2 mutations have a genetic predisposition for developing OC, but not all of these women develop the disease. Epidemiological findings show that lifestyle factors such as contraceptive use and pregnancy, a progesterone dominant state, decrease the risk of getting OC. How ovarian hormones modify the risk of OC is currently unclear. Our study identifies activated Wnt signalling to be a marker for precursor lesions of OC and successfully develops a mouse model that mimics the earliest events in pathogenesis of OC by constitutively activating βcatenin. Using this model and human OC cells, we show that oestrogen promotes and progesterone suppresses the growth of OC cells.
authors: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors: Prathima B
authors: PB
authors: Nagendra
authors: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors: Jyoti
authors: J
authors: Goad
authors: Hunter Cancer Biobank, University of Newcastle, Callaghan, New South Wales, Australia.
authors: Sarah
authors: S
authors: Nielsen
authors: Hunter Cancer Biobank, University of Newcastle, Callaghan, New South Wales, Australia.|School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.|Hunter Area Pathology Services, Calvary Mater Newcastle, Waratah, New South Wales, Australia.
authors: Loui
authors: L
authors: Rassam
authors: School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.|Department of Medical Oncology, Gynaecology Oncology, Calvary Mater Newcastle, Waratah, New South Wales, Australia.
authors: Janine M
authors: JM
authors: Lombard
authors: School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.|Gynaecology and Obstetrics, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
authors: Pravin
authors: P
authors: Nahar
authors: Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
authors: Pradeep S
authors: PS
authors: Tanwar
mesh_terms: D000328:Adult; D000818:Animals; D063646:Carcinogenesis; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004967:Estrogens; D051176:beta Catenin; D011374:Progesterone
keywords: BRCA1/2; Wnt; fallopian tube; hormone; ovarian cancer