Journal
ONCOGENE
Volume 34, Issue 3, Pages 299-309Publisher
SPRINGERNATURE
DOI: 10.1038/onc.2013.562
Keywords
elafin; ovarian cancer; basal-like breast cancer; mitogen; MAP kinase
Funding
- NIH/NCI SPORE in OC [OC P50-CA105009, U01 CA-152990, R21 CA-156021]
- NIH/NINDS [P01 NS047572]
- Honorable Tina Brozman 'Tina's Wish' Foundation
- Dr Miriam and Sheldon G. Adelson Medical Research Foundation
- Robert and Debra First Fund
- Gamel Family Fund
- Ovarian Cancer Research Fund
- Madeline Franchi Ovations for the Cure Fund
- Mary Kay Foundation
- Sandy Rollman Ovarian Cancer Foundation
- Dana-Farber Cancer Institute (DFCI) Strategic Initiative
- Executive Council of the Cancer Foundation
- New Jersey Commission on Cancer Research
- Arthur Sachs/Fulbright/Harvard
- La Fondation Philippe
- La Fondation de France-Recherche clinique en cancerologie-Aide a la mobilite des chercheurs
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High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients. Elafin confers a proliferative advantage to tumor cells through the activation of the MAP kinase pathway. This mitogenic effect can be neutralized by RNA interference, specific antibodies and a MEK inhibitor. Elafin expression in patient-derived samples was also associated with chemoresistance and strongly correlates with bcl-xL expression. We extended these findings into the examination of 1100 primary breast tumors and six breast cancer cell lines. We observed that Elafin is overexpressed and secreted specifically by BLBC tumors and cell lines, leading to a similar mitogenic effect through activation of the MAP kinase pathway. Here too, Elafin overexpression is associated with poor overall survival, suggesting that it may serve as a biomarker and therapeutic target in this setting.
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