Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Jeon, Hye-Min; Jin, Xun; Lee, Joong-Seob; Oh, Se-Yeong; Sohn, Young-Woo; Park, Hyo-Jung; Joo, Kyeung Min; Park, Woong-Yang; Nam, Do-Hyun; DePinho, Ronald A.; Chin, Lynda; Kim, Hyunggee

doi:10.1101/gad.1668708

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Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

Jeon, Hye-Min;
Jin, Xun;
Lee, Joong-Seob;
Oh, Se-Yeong;
Sohn, Young-Woo;
... Kim, Hyunggee;
외 6명

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초록

Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf(-/)-astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.

키워드

Id4; Ink4a/Arf(-/-) astrocyte; notch signaling; cyclin E; neural stem-like cells; glioblastoma; NEURAL STEM-CELLS; ID4; GLIOBLASTOMA; EXPRESSION; BIOLOGY; CANCER

제목: Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling

저자: Jeon, Hye-Min; Jin, Xun; Lee, Joong-Seob; Oh, Se-Yeong; Sohn, Young-Woo; Park, Hyo-Jung; Joo, Kyeung Min; Park, Woong-Yang; Nam, Do-Hyun; DePinho, Ronald A.; Chin, Lynda; Kim, Hyunggee

DOI: 10.1101/gad.1668708

발행일: 2008-08-01

유형: Article

저널명: Genes and Development

권: 22

호: 15

페이지: 2028 ~ 2033