Src as a novel therapeutic target for endometriosis

Kate Lawrenson, Nathan Lee, Lee N, Torres HA, Hugo A. M. Torres, Lee JM, Janet M. Lee, Brueggmann D, Doerthe Brueggmann, Priya Rao, P Nagesh Rao, Rao PN, Houtan Noushmehr, Noushmehr H, Gayther SA, Simon A. Gayther
Gynecologic Oncology · 2014 · vol. 135(1) , pp. 100–107 · doi:10.1016/j.ygyno.2014.06.016 · PMID:24972189 · W2005388734
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This study investigated the role of Src in endometriosis and identified it as a potential therapeutic target.

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Abstract

BACKGROUND: Endometriosis is a common condition that is associated with an increased risk of developing ovarian carcinoma. Improved in vitro models of this disease are needed to better understand how endometriosis, a benign disease, can undergo neoplastic transformation, and for the development of novel treatment strategies to prevent this progression. METHODS: We describe the generation and in vitro characterization of novel TERT immortalized ovarian endometriosis epithelial cell lines (EEC16-TERT). RESULTS: Expression of TERT alone was sufficient to immortalize endometriosis epithelial cells. TERT immortalization induces an epithelial-to-mesenchymal transition and perturbation in the expression of genes involved in the development of ovarian cancer. EEC16-TERT was non-tumorigenic when xenografted into immunocompromised mice but grew in anchorage-independent growth assays in an epidermal growth factor and hydrocortisone dependent manner. Colony formation in agar was abolished by inhibition of Src, and the Src pathway was found to be activated in human endometriosis lesions. CONCLUSIONS: This new in vitro model system mimics endometriosis and the early stages of neoplastic transformation in the development of endometriosis associated ovarian cancer. We demonstrate the potential clinical relevance of this model by identifying Src activation as a novel pathway in endometriosis that could be targeted therapeutically, perhaps as a novel strategy to manage endometriosis clinically, or to prevent the development of endometriosis-associated ovarian cancer.

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Condition tags

endometriosis

MeSH descriptors

Cell Transformation, Neoplastic Cell Transformation, Neoplastic Endometriosis Endometriosis Genes, src Ovarian Diseases Ovarian Diseases Ovarian Neoplasms Ovarian Neoplasms Animals Animals Cells, Cultured Cells, Cultured Endometriosis Endometriosis Endometriosis Epithelial Cells Epithelial Cells Female Female

Citation neighborhood (2-hop)

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (49)

Cited by (7)

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