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ADAMTS16 mutations sensitize ovarian cancer cells to platinum-based chemotherapy
Ist Teil von
Oncotarget, 2017-10, Vol.8 (51), p.88410-88420
Ort / Verlag
United States: Impact Journals LLC
Erscheinungsjahr
2017
Link zum Volltext
Quelle
EZB-FREE-00999 freely available EZB journals
Beschreibungen/Notizen
Ovarian cancer is one of the most lethal malignant tumors in women. The prognosis of ovarian cancer patients depends, in part, on their response to platinum-based chemotherapy. Our recent analysis of genomics and clinical data from the Cancer Genome Atlas demonstrated that somatic mutations of ADAMTS 1, 6, 8, 9, 15, 16, 18 and L1 genes were associated with higher sensitivity to platinum and longer progression-free survival, overall survival, and platinum-free survival duration in 512 patients with high-grade serous ovarian carcinoma. Among the
mutations
is the most commonly affected gene in ovarian cancer. However, the functional role of these mutations in ovarian cancer cells is largely unknown. We performed
studies to compare the functional effects of the six identified ADAMTS missense mutations on the platinum sensitivity of ovarian cancer cells. We also used a well-characterized
mouse model to evaluate the response of ovarian cancer cells with
mutations to platinum-based therapy. Our results showed that exogenously expressed
missense mutations inhibited cell growth or sensitized tumor cells to cisplatin and inhibited tumor growth
. Orthotopic xenograft experiments showed that mice injected with ovarian cancer cells that exogenously expressed
mutations had a better response to cisplatin treatment. Thus, these functional studies provide evidence that mutations of
actively contribute to therapeutic response in ovarian cancer.