Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras

Lee, Joong Seob; Gil, Jung Eun; Kim, Jong Hoon; Kim, Tae Kyung; Jin, Xun; Oh, Seungmin; Sohn, Young Woo; Jeon, Hye Min; Park, Hyo Jung; Park, Jong‐Whi; Shin, Yong Jae; Chung, Yong Gu; Lee, Jang Bo; You, Seungkwon; Kim, Hyunggee

doi:10.1016/j.bbrc.2007.11.005

Cited by 28 publications

(17 citation statements)

References 20 publications

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“…The balance between self-renewal and differentiation of neuroblasts is achieved by the control of asymmetric division at multiple levels: the expression of cell fate determinants; the polarized distribution of these cell fate determinants; and the orientation of the mitotic spindle. Studies in the past several years have shown that neuroblasts may start neoplastic growth when this balance is shifted toward self-renewal due to the lack of cell fate determinants that promote differentiation [43][44][45][46], the failure to achieve polarized distribution of cell fate determinants [39,47], or the misorientation of the mitotic spindle [48][49][50]. These studies suggest that mutations that increase self-renewal may convert normal NSCs to cancer cells.…”

Section: Origin Of Brain Tumor Stem Cellsmentioning

confidence: 94%

Brain Tumor Stem Cells

Xie

2009

Neurochem Res

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Primary malignant brain cancer, one of the most deadly diseases, has a high rate of recurrence after treatment. Studies in the past several years have led to the hypothesis that the root of the recurrence may be brain tumor stem cells (BTSCs), stem-like subpopulation of cells that are responsible for propagating the tumor. Current treatments combining surgery and chemoradiotherapy could not eliminate BTSCs because these cells are highly infiltrative and possess several properties that can reduce the damages caused by radiation or anti-cancer drugs. BTSCs are similar to NSCs in molecular marker expression and multi-lineage differentiation potential. Genetic analyses of Drosophila CNS neoplasia, mouse glioma models, and human glioma tissues have revealed a link between increased NSC self-renewal and brain tumorigenesis. Furthermore, data from various rodent models of malignant brain tumors have provided compelling evidence that multipotent NSCs and lineage-restricted neural progenitor cells (NPCs) could be the cell origin of brain tumors. Thus, the first event of brain tumorigenesis might be the occurrence of oncogenic mutations in the stem cell self-renewal pathway in an NSC or NPC. These mutations convert the NSC or NPC to a BTSC, which then initiates and sustains the growth of the tumor. The self-renewal of BTSCs is controlled by several evolutionarily conserved signaling pathways and requires an intact vascular niche. Targeting these pathways and the vascular niche could be a principle in novel brain tumor therapies aimed to eliminate BTSCs.

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Section: Origin Of Brain Tumor Stem Cellsmentioning

confidence: 94%

Brain Tumor Stem Cells

Xie

2009

Neurochem Res

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“…In this study, both the PI3K/Akt and MEK/ERK pathways were activated by mutant Ras. Signalling via MEK/ERK was required for neurosphere formation in p53-deficient astrocytes, while the PI3K/Akt pathway was necessary for oncogenic transformation [174]. In addition to Stat3 activation, the binding of LIF to its receptor results in the activation of the Ras/Raf/MEK/ ERK pathway via the activation of Sos.…”

Section: Clinical Relevance Of Breast Cancer Stem Cell Theory and Impmentioning

confidence: 99%

Cancer stem cells in breast cancer and metastasis

Lawson

Blatch

Edkins

2009

Breast Cancer Res Treat

109

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The cancer stem cell theory poses that cancers develop from a subset of malignant cells that possess stem cell characteristics and has been proposed to account for the development of a variety of malignancies, including breast cancer. These cancer stem cells (CSC) possess characteristics of both stem cells and cancer cells, in that they have the properties of self-renewal, asymmetric cell division, resistance to apoptosis, independent growth, tumourigenicity and metastatic potential. A CSC origin for breast cancer can neatly explain both the heterogeneity of breast cancers and the relapse of the tumours after treatment. However, many reports on CSC in the breast are contradictory. There is variation with respect to how breast cancer stem cells should be identified, their characteristics and a possible lack of correlation between clinical outcome and breast cancer stem cell status of a tumour. These combined factors have made breast cancer stem cells a highly contentious issue. In this review, we highlight the progress in the analysis of cancer stem cells, with an emphasis on breast cancer.

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“…occur simultaneously, they promote the generation of brain cancer stem-like cells in vitro (Lee et al, 2008).…”

Section: Research Articlementioning

confidence: 99%

Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells

Santoriello

Deflorian

Pezzimenti

et al. 2009

Disease Models &Amp; Mechanisms

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SUMMARYConstitutively active, 'oncogenic' H-RAS can drive proliferation and transformation in human cancer, or be a potent inducer of cellular senescence. Moreover, aberrant activation of the Ras pathway owing to germline mutations can cause severe developmental disorders. In this study we have generated transgenic zebrafish that constitutively express low levels, or can be induced to express high levels, of oncogenic H-RAS. We observed that fish carrying the integrated transgene in their germline display several hallmarks of Costello syndrome, a rare genetic disease caused by activating mutations in the gene H-RAS, and can be used as a model for the disease. In Costello-like fish, low levels of oncogenic H-RAS expression are associated with both reduced proliferation and an increase in senescence markers in adult progenitor cell compartments in the brain and heart, together with activated DNA damage responses. Overexpression of H-RAS through a heat-shock-inducible promoter in larvae led to hyperproliferation, activation of the DNA damage response and tp53-dependent cell cycle arrest. Thus, oncogene-induced senescence of adult proliferating cells contributes to the development of Costello syndrome and provides an alternative pathway to transformation in the presence of widespread constitutively active H-RAS expression.

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Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras

Cited by 28 publications

References 20 publications

Brain Tumor Stem Cells

Brain Tumor Stem Cells

Cancer stem cells in breast cancer and metastasis

Expression of H-RASV12 in a zebrafish model of Costello syndrome causes cellular senescence in adult proliferating cells

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