Up-regulation of genes involved in the Insulin signalling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link Polycystic Ovarian Syndrome and endometrial cancer

Shafiee, Mohamad Nasir; Seedhouse, Claire; Mongan, Nigel; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William

Abstract

BACKGROUND

Endometrial cancer (EC) is the most common gynaecological cancer amongst women in the UK. Although previous studies have found that women with polycystic ovary syndrome (PCOS) have at least a three-fold increase in endometrial cancer (EC) risk compared to women without PCOS, the precise molecular mechanisms which link between PCOS and EC remain unclear. It has been suggested that insulin resistance may contribute to the increased risk of EC in PCOS. The specific expression of genes related to the insulin-signalling pathway including the IGF system in the endometrium of women with PCOS has however never been measured and compared to that in women with EC without PCOS and control women without EC or PCOS. .

OBJECTIVES

To test the hypothesis that insulin signaling plays a key role in the development of EC in women with PCOS by measuring and comparing the expression of three key genes involved in the insulin signaling pathway (IGF1, PTEN and IGFBP1) in endometrial tissue obtained from three groups of women; PCOS without EC, women with EC without PCOS and non-PCOS women without EC (controls). We also aimed to determine the correlation between the gene expressions to various clinical variables among participants.

METHODS

This was a cross-sectional study of 102 women in 3 groups (PCOS, EC and controls) at a University teaching hospital in the United Kingdom. Clinical assessment (blood pressure, body mass index (BMI) and waist-hip-circumference ratio), venepuntures (fasting blood sugar, insulin, lipid profile, hormones) and endometrial tissue biopsies were taken in all participants. Endometrial tissue RNA extraction was performed before real time polymerase-chain-reaction for the genes of interest (IGF1, IGFBP1 and PTEN) was carried out. To compare the baseline characteristics of the study population, One-Way-ANOVA test or the Independent t-test was used. For variables that were not normally distributed, the Spearman correlation test was used to calculate the r value. A "p" value of

Citation

Shafiee, M. N., Seedhouse, C., Mongan, N., Chapman, C., Deen, S., Abu, J., & Atiomo, W. (2016). Up-regulation of genes involved in the Insulin signalling pathway (IGF1, PTEN and IGFBP1) in the endometrium may link Polycystic Ovarian Syndrome and endometrial cancer. Molecular and Cellular Endocrinology, 424, 94-101. https://doi.org/10.1016/j.mce.2016.01.019

• Journal Article Type: Article
• Acceptance Date: Jan 20, 2016
• Online Publication Date: Jan 21, 2016
• Publication Date: Mar 15, 2016
• Deposit Date: Jan 28, 2016
• Publicly Available Date: Jan 28, 2016
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Electronic ISSN: 1872-8057
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 424
• Pages: 94-101
• DOI: https://doi.org/10.1016/j.mce.2016.01.019
• Keywords: Endometrial cancer; IGF1; IGFBP1; PCOS; PTEN
• Public URL: https://nottingham-repository.worktribe.com/output/772183
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0303720716300193