title: Src as a novel therapeutic target for endometriosis.
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.
authors: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA. Electronic address: Kate.Lawrenson@med.usc.edu.
authors: Kate
authors: K
authors: Lawrenson
authors: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA. Electronic address: nathanl@usc.edu.
authors: Nathan
authors: N
authors: Lee
authors: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Núcleo de Apoio à Pesquisa (NAP) denominado Centro de Biologia Sistêmica Integrada (CISBi), São Paulo, Brazil.
authors: Hugo A M
authors: HA
authors: Torres
authors: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA. Electronic address: janetmle@usc.edu.
authors: Janet M
authors: JM
authors: Lee
authors: Department of Obstetrics and Gynecology, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA. Electronic address: brueggma@usc.edu.
authors: Doerthe
authors: D
authors: Brueggmann
authors: Pathology and Lab Medicine, David Geffen University of California Los Angeles, 22-26 Rehab Cntr, 1000 Veteran Ave, Los Angeles, CA 90024, USA. Electronic address: nrao@ucla.edu.
authors: P Nagesh
authors: PN
authors: Rao
authors: Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Núcleo de Apoio à Pesquisa (NAP) denominado Centro de Biologia Sistêmica Integrada (CISBi), São Paulo, Brazil. Electronic address: houtan@fmrp.usp.br.
authors: Houtan
authors: H
authors: Noushmehr
authors: Department of Preventive Medicine, University of Southern California/Keck School of Medicine, 1450 Biggy Street, Los Angeles, CA 90033, USA. Electronic address: gayther@usc.edu.
authors: Simon A
authors: SA
authors: Gayther
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D004847:Epithelial Cells; D005260:Female; D016391:Genes, src / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051379:Mice; D010049:Ovarian Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
keywords: Clear cell ovarian cancer; Endometriosis; Endometriosis epithelial cells; In vivo xenograft; Src; Three-dimensional in vitro modeling