Ovarian hormones through Wnt signalling regulate the growth of human and mouse ovarian cancer initiating lesions

// Prathima B. Nagendra 1 , Jyoti Goad 1 , Sarah Nielsen 2 , Loui Rassam 2,3,4 , Janine M. Lombard 3,5 , Pravin Nahar 3,6 and Pradeep S. Tanwar 1 1 Gynaecology Oncology Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia 2 Hunter Cancer Biobank, University of Newcastle, Callaghan, New South Wales, Australia 3 School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia 4 Hunter Area Pathology Services, Calvary Mater Newcastle, Waratah, New South Wales, Australia 5 Department of Medical Oncology, Gynaecology Oncology, Calvary Mater Newcastle, Waratah, New South Wales, Australia 6 Gynaecology and Obstetrics, John Hunter Hospital, New Lambton Heights, New South Wales, Australia Correspondence to: Pradeep S. Tanwar, email: // Keywords : BRCA1/2, Wnt, ovarian cancer, hormone, fallopian tube Received : August 15, 2016 Accepted : August 21, 2016 Published : August 30, 2016 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.