Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours

M. H. Chen, W. K. Yang, J. Whang-Peng, L. S. Lee, T. S. Huang

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 60 nM. 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.

Original languageEnglish
Pages (from-to)171-182
Number of pages12
JournalApoptosis
Volume3
Issue number3
Publication statusPublished - Dec 1 1998
Externally publishedYes

Fingerprint

Glial Fibrillary Acidic Protein
Tumors
Butyric Acid
Apoptosis
Astrocytoma
Neoplasms
Primary Cell Culture
Cell culture
Cells
Intermediate Filament Proteins
Carmustine
Cell growth
Gene expression
Lethal Dose 50
Tetradecanoylphorbol Acetate
Astrocytes
Colonic Neoplasms
Leukemia
Tissue
Staining and Labeling

Keywords

  • 12-o-tetradecanoylphorbol-13-acetate (TPA)
  • Bicnu™
  • Differentiation
  • Glial fibrillary acidic protein (GFAP)
  • Phenylacetate
  • Sodium butyrate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours. / Chen, M. H.; Yang, W. K.; Whang-Peng, J.; Lee, L. S.; Huang, T. S.

In: Apoptosis, Vol. 3, No. 3, 01.12.1998, p. 171-182.

Research output: Contribution to journalArticle

Chen, M. H. ; Yang, W. K. ; Whang-Peng, J. ; Lee, L. S. ; Huang, T. S. / Differential inducibilities of GFAP expression, cytostasis and apoptosis in primary cultures of human astrocytic tumours. In: Apoptosis. 1998 ; Vol. 3, No. 3. pp. 171-182.
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