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J. Biol. Chem., Vol. 266, Issue 2, 728-734, 01, 1991
RS Morrison
Basic fibroblast growth factor (bFGF) is a heparin-binding protein
expressing potent mitogenic and angiogenic properties. Elevated levels of
bFGF have recently been described in human glioma cell lines. The high
degree of vascularity and invasiveness which characterize human gliomas
suggest that activated expression of bFGF or similar proteins may be
related to the aberrant growth patterns of these tumors. The influence of
endogenous bFGF on glioma cell growth in vitro was evaluated in the present
study by down-regulating bFGF expression using antisense oligonucleotide
primers. The addition of 50 microM bFGF- specific antisense primer to the
human glioma cell line SNB-19 resulted in an 80% inhibition in glioma
growth. This effect was saturable and specific. Antisense primers directed
to two different sites of bFGF mRNA were effective in suppressing SNB-19
growth, whereas sense strand primer was ineffective. Furthermore, only the
antisense primer significantly reduced the specific activity of bFGF
protein in SNB-19 cell extracts. Neither antisense or sense primers
inhibited the growth of non-transformed human glia. bFGF mRNA was detected
in both transformed and non-transformed human glia by polymerase chain
reaction analysis suggesting that alterations in bFGF isoform content or
activity may be specifically related to abnormal growth control in human
gliomas.
Suppression of basic fibroblast growth factor expression by antisense oligodeoxynucleotides inhibits the growth of transformed human astrocytes
Robert S. Dow Neurological Sciences Institute, Good Samaritan Hospital, Portland, Oregon 97209.
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