Correlation of B-FABP and GFAP expression in malignant glioma

Abstract

The murine brain fatty acid binding protein (B-FABP) is encoded by a developmentally regulated gene that is expressed in radial glial cells and immature astrocytes. We have cloned the human B-FABP gene and have mapped it to chromosome 6q22-23. We show that B-FABP mRNA is expressed in human malignant glioma tumor biopsies and in a subset of malignant glioma cell lines, as well as in human fetal retina and brain. Malignant glioma tumors are characterized by cytoplasmic bundles of glial ®brillary acidic protein (GFAP), a protein normally expressed in mature astrocytes. Establishment of malignant glioma cell lines often results in loss of GFAP. The subset of malignant glioma cell lines that express GFAP mRNA also express B-FABP mRNA. Co-localization experiments in cell lines indicate that the same cells produce both GFAP and B-FABP. We suggest that some malignant gliomas may be derived from astrocytic precursor cells which can express proteins that are normally produced at di erent developmental stages in the astrocytic di erentiation pathway.

Regulation of Brain Fatty Acid-binding Protein Expression by Differential Phosphorylation of Nuclear Factor I in Malignant Glioma Cell Lines

“…Region-We have previously shown that the human B-FABP gene is contained within a 4.5-kb region on chromosome 6q22-23 (9). To study the regulation of B-FABP transcription, we first mapped the transcription initiation site by primer extension.…”

“…FABP gene has been previously described (9). A 3-kb EcoRI fragment containing exons I, II, and 1.8 kb of 5Ј-flanking DNA was subcloned into pBluescript and sequenced.…”

“…Co-expression of GFAP and B-FABP in the same malignant glioma cells (9) therefore suggests that these tumors are derived from cells that have the potential of expressing proteins that are normally produced at different stages in the glial differentiation pathway. We are studying the regulation of the B-FABP gene in order to identify transcription factors involved in the regulation of glial genes in malignant glioma and understand the basis for the variation in B-FABP expression in different malignant glioma lines.…”

“…We have previously shown that GFAP(ϩ) malignant glioma lines express a second glial cell marker, brain fatty acid-binding protein (B-FABP) (9). Of 15 malignant glioma lines tested, 5 co-expressed B-FABP and GFAP, 8 expressed neither gene, while 2 had low levels of B-FABP and undetectable levels of GFAP.…”

Calcineurin Regulates Nuclear Factor I Dephosphorylation and Activity in Malignant Glioma Cell Lines

“…Cell Lines, Constructs, Chemicals, and Transfections-The human MG cell lines have been previously described (6,16). All cell lines were cultured in Dulbecco's modification of Eagle's minimum essential medium supplemented with 10% fetal calf serum, penicillin (100 units/ml), and streptomycin (100 g/ml).…”