Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.
Chemotherapy-Induced Depletion of OCT4-Positive Cancer Stem Cells in a Mouse Model of Malignant Testicular Cancer.
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DOI：
10.1016/j.celrep.2017.10.078
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发表时间：
2017-11-14
期刊：
影响因子：
8.8
通讯作者：
Weiss RS
中科院分区：
文献类型：
--
作者：
Pierpont TM;Lyndaker AM;Anderson CM;Jin Q;Moore ES;Roden JL;Braxton A;Bagepalli L;Kataria N;Hu HZ;Garness J;Cook MS;Capel B;Schlafer DH;Southard T;Weiss RS
Testicular germ cell tumors (TGCTs) are among the most responsive solid cancers to conventional chemotherapy. To elucidate the underlying mechanisms, we developed a mouse TGCT model featuring germ cell-specific Kras activation and Pten inactivation. The resulting mice developed malignant, metastatic TGCTs composed of teratoma and embryonal carcinoma, the latter of which exhibited stem cell characteristics, including expression of the pluripotency factor OCT4. Consistent with epidemiological data linking human testicular cancer risk to in utero exposures, embryonic germ cells were susceptible to malignant transformation, whereas adult germ cells underwent apoptosis in response to the same oncogenic events. Treatment of tumor-bearing mice with genotoxic chemotherapy not only prolonged survival and reduced tumor size, but selectively eliminated the OCT4-positive cancer stem cells. We conclude that the chemosensitivity of TGCTs derives from the sensitivity of their cancer stem cells to DNA-damaging chemotherapy.
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影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
64.5
作者：
Barlow JH;Faryabi RB;Callén E;Wong N;Malhowski A;Chen HT;Gutierrez-Cruz G;Sun HW;McKinnon P;Wright G;Casellas R;Robbiani DF;Staudt L;Fernandez-Capetillo O;Nussenzweig A
通讯作者：
Nussenzweig A
影响因子：
1.5
作者：
Lesche, R;Groszer, M;Wu, H
通讯作者：
Wu, H
影响因子：
8
作者：
Bartkova, J.;Horejsi, Z.;Bartek, J.
通讯作者：
Bartek, J.
DOI：
10.1073/pnas.91.25.12258
发表时间：
1994-12-06
影响因子：
11.1
作者：
FUJIWARA, Y;KOMIYA, T;NOCE, T
通讯作者：
NOCE, T