A NOVEL GROWTH-STIMULATING ACTIVITY FROM BRL-3A CELL-CONDITIONED MEDIUM

The R- cell line is a 3T3-like cell line originating from mouse embryo s with a homozygous disruption of the type 1 insulin-like growth facto r receptor (IGF-IR) genes. Although R- cells cannot grow at all in ser um-free medium (SFM) supplemented by several known growth factors, eit her singly or in combination, they are able to grow in 10% serum, albe it at a reduced rate. These findings suggested that serum contains an unknown, or unidentified, growth factor that can promote cell growth e ven in cells devoid of IGF-IRs. In an effort to identify such growth f actor, we searched, using R- cells, for a growth and DNA synthesis sti mulating activity in SFM conditioned by different cell lines. We found that the BRL-3A cell line secreted an activity capable of stimulating DNA synthesis and cell proliferation in R- cells. This activity (whic h is concentration-dependent) can be collected and concentrated by ult rafiltration, it is heat-labile, proteinase K-sensitive and has a size larger than 10 kDa. Because of the resistance of R- cells to stimulat ion by known growth factors, we believe that this activity is due to a novel polypeptide secreted by BRL-3A cells. Further characterization of the active component(s) is in progress.