Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours |
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Authors: | M-H Chen W K Yang J Whang-Peng L-S Lee T-S Huang |
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Institution: | Department of Neurosurgery, Veterans General Hospital-Taipei and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China. |
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Abstract: | Glial fibrillary acidic protein (GFAP) is an astrocytic lineage-specific intermediate filament protein, and its expression
or non-expression is inversely correlated with the tumourigenecity of astrocytoma cells. To estimate the GFAP levels of astrocytes
in intracranial tumour tissues, we established primary cultures from six astrocytic tumour specimens and used a double-staining
flow cytometric method to detect the different levels of GFAP among these primary cultures. Although these primary cultures
exhibited the same Matrigel invasiveness, their GFAP expression is inversely related to the rate of cell growth and the histologic
grade of the original tumour. Phenylacetate, 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate, which are potent
inducers of differentiation in various cancer cells, have been examined for their effects on these primary cultures. Cytostasis
was more or less caused by these compounds in all six primary cultures, but induction of GFAP was observed only in the primary
culture derived from a less malignant astrocytoma specimen having the highest intrinsic GFAP level. Interestingly, this primary
culture, but not others, also exhibited increased HRG-α expression after phenylacetate or sodium butyrate treatment. Loss
of the inducibility of differentiation-related gene expression could be one of the events involved in the malignant progression
of astrocytomas. In addition, the chemotherapeutic agent BiCNU has a killing effect on all six primary culture cells, with
LD50 less than 60nM. The underlying mechanism was through the induction of apoptosis in these primary culture cells regardless
of their varying malignancies of original tumours. However, unlike colon cancer and leukaemia cells, sodium butyrate could
not induce apoptosis within 4 days in these astrocytic tumour cells, indicating that the cell context of different cell types
indeed determined the ability of sodium butyrate to induce apoptosis.
This revised version was published online in June 2006 with corrections to the Cover Date. |
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Keywords: | 12-O-tetradecanoylphorbol-13-acetate (TPA) BiCNUTM differentiation glial fibrillary acidic protein (GFAP) phenylacetate sodium butyrate |
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