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[P2.71]: The function of c‐kit , cip2a and c‐myc in neural progenitor and glioblastoma cells
Author(s) -
Fox H.M.A.,
Kerosuo L.,
Wartiovaara K.
Publication year - 2008
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2008.09.196
Subject(s) - glioblastoma , library science , citation , neural stem cell , computer science , medicine , biology , cancer research , stem cell , genetics
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumour, and usually leads to a death of the patient within 2 years of diagnosis. GBM belongs to glioma family, the most common type of primary central nervous system (CNS) tumours that arises from glial cells. It has been hypothesized that all tumours contains a small amount of cancer stem cells (CSCs) fromwhich the tumours originate, and which are related to neural progenitor cells (NPCs). Both CSCs and NPCs are primitive, highly proliferating cells that maintain the self-renewing capacity of the host tissue. The difference is the regulation of these properties, which is disturbed in the former ones and can lead to uncontrolled tissue growth. Before GBMs can be ameliorated, their origin and the characters of CSCs must be known. We have shown that important proto-oncogenes c-myc, cip2a and c-kit promotes primitive characters in NPCs or in astrocytes. Now we have several GBM-derived cell lines under study, and some of these lines show an elevated c-kit expression. Also increased c-myc and cip2a activities are hypothesized to occur in these same lines. The primitivity of these different cell lines is to be measured by proliferation and self-renewal assays. The most aggressive lines – showing increased proto-ongogene expression, proliferation and self-renewal – are injected to the nude mice and their in vivo tumour-forming capacity is investigated. In addition, shRNA constructs will be used for silencing preceding protooncogenes and the effect on primitive characters and tumourigenicity is to be studied as described above. In order to find the CSCs in these heterogenic tumour cell populations we will use a potential CSC marker CD133. This study will give some insights to glioma biology and pathogenity. Potential findings concerning the role of c-myc, cip2a and c-kit possibly serves a relevant target for novel therapeutics.