regulation of human glioblastoma T98G cells by insulin-like growth factor-1 and
Ambrose D, Resnicoff M, Coppola D, Sell C, Miura M, Jameson S, Baserga R,
Department of Pathology, Jefferson Medical College, Philadelphia,
The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is
an important step in the control of cell proliferation and development.
In particular, IGF-1 and IGF-2 are key regulators of central nervous system
development, and may modulate the growth of glial tumors.
We have investigated the growth factor regulation of the human glioblastoma cell
These cells growth arrested in serum-free medium at 34 degrees C, despite their
secretion of substantial amounts of bioactive IGF-1.
To be stimulated to divide, growth-arrested cells required the addition of
platelet-derived growth factor (PDGF) or its equivalent, 1% serum.
Cell proliferation in serum-free medium could also be obtained by shifting the
cells to a temperature of 39.6 degrees C.
Treatment of growth-arrested cells with PDGF or temperature shift was
accompanied by a transient increase in the expression of the mRNA for the IGF-1
Transfection with a plasmid constitutively expressing the full cDNA for the
human IGF-1 receptor allowed autonomous growth in serum-free medium at 34
By contrast, growth induction by growth factors or temperature shift was
abrogated by transfection of the cells with a plasmid expressing a 300 bp
segment of mRNA antisense to the IGF-1 receptor mRNA.
Cloning in soft agar was also inhibited by expression of antisense IGF-1
These results demonstrate that the IGF-1 receptor is strictly required for the
growth of T98G glioblastoma cells.
Moreover, the autocrine interaction of IGF-1 with its receptor regulates both
autonomous and anchorage-independent growth of these cells.
PMID: 8138595 [PubMed - indexed for MEDLINE]