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dc.contributor.authorManek, Roxanne
dc.contributor.authorPakzamir, Elham
dc.contributor.authorMhawech-Fauceglia, Paulette
dc.contributor.authorPejovic, Tanja
dc.contributor.authorSowter, Heidi M.
dc.contributor.authorGayther, Simon A.
dc.contributor.authorLawrenson, Kate
dc.date.accessioned2017-04-13T09:14:59Z
dc.date.available2017-04-13T09:14:59Z
dc.date.issued2016-08-15
dc.identifier.citationManek, R. et al (2016) 'Targeting Src in endometriosis-associated ovarian cancer' Oncogenesis, 5 (8):e251en
dc.identifier.issn21579024
dc.identifier.doi10.1038/oncsis.2016.54
dc.identifier.urihttp://hdl.handle.net/10545/621543
dc.description.abstractThe SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.
dc.description.sponsorshipN/Aen
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/oncsis.2016.54en
dc.rightsArchived with thanks to Oncogenesisen
dc.subjectOvarian canceren
dc.subjectSRC proto-oncogeneen
dc.subjectOncologyen
dc.subjectCancer treatmenten
dc.titleTargeting Src in endometriosis-associated ovarian canceren
dc.typeArticleen
dc.contributor.departmentUniversity of Southern Californiaen
dc.contributor.departmentOregon Health and Science Universityen
dc.contributor.departmentUniversity of Derbyen
dc.contributor.departmentSamuel Oschin Comprehensive Cancer Instituteen
dc.identifier.journalOncogenesisen
dcterms.dateAccepted2016-06-20
refterms.dateFOA2019-02-28T15:41:42Z
html.description.abstractThe SRC proto-oncogene is commonly overexpressed or activated during cancer development. Src family kinase inhibitors are approved for the treatment of certain leukemias, and are in clinical trials for the treatment of solid tumors. Src signaling is activated in endometriosis, a precursor of clear cell and endometrioid subtypes of epithelial ovarian cancers (OCs). We examined the expression of phosphorylated Src (Src-pY416) in 381 primary OC tissues. Thirty-six percent of OCs expressed Src-pY416. Src-pY416 expression was most common in endometriosis-associated OCs (EAOCs) (P=0.011), particularly in clear cell OCs where 58.5% of cases expressed Src-pY416. Src-pY416 expression was associated with shorter overall survival (log rank P=0.002). In vitro inhibition of Src signaling using 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2) resulted in reduced anchorage-independent and -dependent growth, and in three-dimensional cell culture models PP2 disrupted aggregate formation in Src-pY416-positive but not in Src-pY416-negative cell lines. These data suggest that targeting active Src signaling could be a novel therapeutic opportunity for EAOCs, and support the further pre-clinical investigation of Src family kinase inhibitors for treating OCs expressing Src-pY416.


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