Regulating the availability of transforming growth factor β1 in B104 neuroblastoma cells

Transforming growth factor (TGF) β1 is a key player in early brain development, hence, its availability (i.e., synthesis and release) affects neuronogenesis. TGFβ1 moves proliferating cells out of the cell cycle and promotes their subsequent migration. The present study tested the hypothesis that neural progenitors self-regulate TGFβ1. B104 neuroblastoma cells which can grow in the absence of serum or growth factors were used in systematic studies of transcription, translation, release, and activation. These studies relied on quantitative enzyme-linked immunosorbent assays and real-time polymerase chain reactions. TGFβ1 positively upregulated its own intracellular expression and promoted increased release of TGFβ1 from cells. The induction of TGFβ1 was independent of a change in transcription, but it depended on cycloheximide-inhibited translation. Signaling mediated by downstream Smad2/3 through the TGFβ receptors and intracellular protein transport were also required for release of TGFβ1 from B104 cells. Thus, TGFβ1 production and release were mediated through a feed-forward mechanism and were pivotally regulated at the level of translation. These activities appear to be key for the role of TGFβ1 in the proliferation and migration of young neurons.