A role for SOX9 and Wnt-related proteins in endometrial adenocarcinoma

Draper, Hannah
A role for SOX9 and Wnt-related proteins in endometrial adenocarcinoma. Master of Philosophy thesis, University of Liverpool.

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Introduction: Endometrial carcinoma is already the most common gynaecological malignancy in the developed world, and by 2015 the incidence is set to be twice that of 2005. Despite this, therapeutic options available for advanced disease are very limited. The canonical Wnt/β-catenin pathway is known to have a key role in homeostasis of normal endometrial cellular proliferation and differentiation, and is also implicated in endometrial proliferative conditions such as carcinogenesis. SOX9 is a postulated Wnt-regulator and may play a key role in establishment and maintenance of characteristic phenotypes of glandular cells during the menstrual cycle. The interaction of Wnt/β-catenin pathway and SOX9 in the endometrium is not known, neither are the effects of ovarian steroids on these pathways and proteins fully elucidated. The expression of a panel of Wnt-related proteins in endometrial cancer tissue samples was compared to normal pre- and post-menopausal endometrium. Further in vitro work investigated the effect of ovarian steroid hormones on SOX9 and steroid receptor expression in a well characterised, well differentiated endometrial carcinoma cell line Ishikawa. Methods: 51 primary endometrial samples (31 endometrial adenocarcinomas (EC), 10 normal proliferative phase (PP) and 10 normal post-menopausal (PM)) were assessed for the expression of SOX9, Ki67, β-catenin, SOX2, SFRS2, and NAP1L1 using immunohistochemistry. The Ishikawa cell line was maintained in phenol-free charcoal stripped media for 72 hours, and then treated with ovarian steroids: estradiol (E2), medroxyprogesterone acetate (MPA), E2 + MPA, basic fibroblast growth factor (FGF), and 5-alpha-dihydrotestosterone (DHT) for 72 hours. RT-PCR was performed for oestrogen receptor α (ER), progesterone receptor (PR), and SOX9. Statistical analysis used the Mann-Whitney and Spearman Rank tests. Results: Nuclear β-catenin was correlated with the Wnt-related proteins SOX2 (p=0.025), NAP1L1 (p=0.046) and SFRS2 (p=0.032). However, none of these proteins demonstrated significantly different expression across the groups. The expression of SOX9 was significantly lower in the proliferative tissues (PP and EC) than the atrophic PM (p

Item Type: Thesis (Master of Philosophy)
Additional Information: Date: 2013-08 (completed)
Subjects: ?? RG ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 06 Aug 2014 11:20
Last Modified: 16 Dec 2022 04:41
DOI: 10.17638/00014815
URI: https://livrepository.liverpool.ac.uk/id/eprint/14815