Details

Autor(en) / Beteiligte

• Yang, Rui
• Chen, Lee H
• Hansen, Landon J
• Carpenter, Austin B
• Moure, Casey J
• Liu, Heng
• Pirozzi, Christopher J
• Diplas, Bill H
• Waitkus, Matthew S
• Greer, Paula K
• Zhu, Huishan
• McLendon, Roger E
• Bigner, Darell D
• He, Yiping
• Yan, Hai

Titel

Cic Loss Promotes Gliomagenesis via Aberrant Neural Stem Cell Proliferation and Differentiation

Ist Teil von

• Cancer research (Chicago, Ill.), 2017-11, Vol.77 (22), p.6097-6108

Ort / Verlag

United States: American Association for Cancer Research, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Inactivating mutations in the transcriptional repression factor ( ) occur in approximately 50% of human oligodendrogliomas, but mechanistic links to pathogenesis are unclear. To address this question, we generated -deficient mice and human oligodendroglioma cell models. Genetic deficiency in mice resulted in a partially penetrant embryonic or perinatal lethal phenotype, with the production of an aberrant proliferative neural population in surviving animals. cultured neural stem cells derived from conditional knockout mice bypassed an EGF requirement for proliferation and displayed a defect in their potential for oligodendrocyte differentiation. is known to participate in gene suppression that can be relieved by EGFR signal, but we found that also activated expression of a broad range of EGFR-independent genes. In an orthotopic mouse model of glioma, we found that loss potentiated the formation and reduced the latency in tumor development. Collectively, our results define an important role for in regulating neural cell proliferation and lineage specification, and suggest mechanistic explanations for how mutations may impact the pathogenesis and therapeutic targeting of oligodendroglioma. .