Biomedical subjects
Publications and source records attributed to T Curran.
Stimulation of fibroblasts with serum or purified growth factors leads to a dramatic induction of expression of both c-fos mRNA and protein within a few minutes, followed by activation of c-myc. This suggests that c-fos induction is a primary event and the earliest known effect on gene expression by growth factors.
Previous studies have suggested a role for c-fos in cellular differentiation in fetal membranes, haematopoietic cells and teratocarcinoma stem cells. In other cell types, such as fibroblasts, c-fos expression is normally very low, but is rapidly induced by peptide growth factors, implicating c-fos in growth control mechanisms. Here, we show that the TPA (12-O-tetradecanoylphorbol-13-acetate)-induced macrophage-like differentiation of HL60 human promyelocytic precursor cells is accompanied by the induction of both c-fos mRNA and protein within 15 min after treatment, suggesting a functional role for c-fos in this differentiation system. In quiescent terminally differentiated macrophages, expression of c-fos is inducible by the macrophage-specific growth factor colony-stimulating factor-1 (CSF-1). The kinetics of c-fos induction, however, are entirely different from those in growth factor-stimulated fibroblasts, supporting the view that the c-fos gene product may serve different functions in different cell types.
There has been much interest in the biochemical and biophysical processes that couple extracellular signals to alterations in gene expression. While many early events associated with the treatment of cells with growth factors have been described (for example, ion flux and protein phosphorylation), it has proved difficult to establish biochemical links to gene expression. Recently, the study of such genomic control signals has been facilitated by the demonstration that the c-fos proto-oncogene is rapidly and transiently induced by treatment of several cell types with polypeptide growth factors and other growth modulating substances. In one particular system it has been shown that nerve growth factor (NGF) causes a transient induction of c-fos in the phaeochromocytoma cell line PC12, within 15 min. Furthermore, the magnitude of this induction can be modulated with pharmacological agents such as peripheral-type benzodiazepines (BZDs). Thus, the study of c-fos expression in PC12 cells could yield valuable clues to the coupling mechanisms linking cell surface activation to genomic events. Here we demonstrate that c-fos is induced in PC12 cells either by receptor-ligand interaction or by agents or conditions that effect voltage-dependent calcium channels.
In their target article on explaining functional deficits in amnesia, Mayes and Downes (this issue) discuss the relevance of implicit memory. Our commentary considers a number of implicit memory phenomena that may be especially pertinent to understanding the functional deficits of amnesia. Recent evidence suggests that amnesic patients do not benefit normally from an exact perceptual match of stimuli between study and text. We propose that this impairment may reflect one manifestation of a more general deficit in associative binding of information across different brain subsystems. This idea helps to clarify the distinction between implicit and explicit memory, and suggests that studies of implicit memory can help to elucidate the functional deficits in amnesia.