The long-term objective of our research is to study the role of junctional cell-to-cell communication in growth control, in particular, the role of alterations in communication in the etiology of cancer. We will now examine the action on junctional communication of several viral oncogenes and cellular proto- oncogenes, in particular, v-src and c-src. We inquire into the mechanisms by the which these oncogenes downregulate communication. We focus on their action on the phosphoinositide messenger route, particularly its diacylglycerol branch exploring how this route controls communication and the role of intracellular Ca in this control. Furthermore, we will investigate the mechanism by which the growth of certain transformed cells is inhibited by junctional communication with normal cells. We test what transformed cell types are susceptible to inhibition, and analyze the kinetics of the inhibitory interaction and its relation to the cell cycle. The basic experiments are carried out on cell cultures; transformation is induced by viruses or recombinant oncogene DNAs. The main approaches involve probing of junctional membrane permeabilities with intracellular fluorescent tracers (fluorescent-labelled peptides and dyes), and microfluorimetric and microluminescence image-intensifier techniques for detection of changes in free Ca concentration, including local changes, inside the cells.
|Zimmerman, A L; Rose, B (1985) Permeability properties of cell-to-cell channels: kinetics of fluorescent tracer diffusion through a cell junction. J Membr Biol 84:269-83|