| Popis: |
Although fibroblast growth factor receptor (FGFR) 4 has been reported not to be expressed in normal human astrocytes, we have demonstrated expression of FGFR-1, -3, and -4 in six human glioblastoma cell lines (SNB19, T98G, UW18, D54 MG, U251MG, and U373MG) by RT-PCR Southern blot analysis. All six lines exhibited predominantly beta-type (with only two extracellular Ig-like domains) FGFR-1 expression. In contrast, FGFR-2 expression was only detected in the UW18 cell line. This evidence support our previous observation that malignant progression in astrocytomas is associated with a shift in FGFR-1 mRNA splicing from the alpha-type (with three extracellular Ig-like domains) to the beta-type with concomitant loss of FGFR-2 expression. It also demonstrates the unique finding that FGFR-4 induction in astrocytomas is associated with transformation. In addition to these cell lines, expression of FGFRs was analyzed in normal human brain tissue and in human astrocytoma tissue samples corresponding to different grades of malignancy. FGFR-4 mRNA was undetectable in normal adult white matter, the site of origin of astrocytomas, while astrocytomas of all grades exhibited significant expression of FGFR-4 mRNA as determined by RT-PCR Southern blot analysis. The proportion of FGFR-4 mRNA did not appear to change in relation to the malignant progression of the astrocytomas. This suggests that induction of FGFR-4 expression in astrocytes represents an early event in their malignant transformation. Induction of FGFR-4 in malignant astrocytomas is consistent with previous reports demonstrating that expression of aFGF, which activates FGFR-4, increases in astrocytomas. The simultaneous induction of FGFR-4 and aFGF may establish a potential autocrine pathway that endows astrocytoma cells with a selective growth advantage. Interestingly, very high expression of FGFR-4 mRNA was found in human fetal brain tissue. The above findings suggest that the malignant transformation of astrocytes may involve the activation of a fetal growth promoting pathway. |
