AJP - Renal Physiology, Vol 252, Issue 6 1175-F1179, Copyright © 1987 by American Physiological Society
ADP activates protooncogene expression in renal epithelial cells
S. Kartha, V. P. Sukhatme and F. G. Toback
Purine nucleotides, particularly adenosine diphosphate (ADP), are the most
potent mitogens known for monkey kidney epithelial cells of the BSC-1 line.
To explore the molecular mechanisms by which ADP exerts its mitogenic
effect, we tested the hypothesis that stimulation of DNA synthesis in these
renal cells is mediated by activation of protooncogenes. Transcripts of the
c-Ha-ras protooncogene were identified in quiescent, high density cells.
Addition of ADP to the culture medium stimulated protooncogene expression
fourfold. Maximal expression of c-ras was observed by 12 h after exposure
to ADP, and preceded the initiation of DNA synthesis. Expression of the
c-myc protooncogene was not detected in unstimulated cells, but accumulated
maximally after 1 h of exposure to ADP. As with ADP-stimulated expression
of the c-ras protooncogene, transcripts of the transferrin receptor gene
reached a maximal value at 12 h, whereas the abundance of gamma-actin mRNA
was not altered for up to 24 h. The results indicate that exogenous ADP
stimulates protooncogene expression before initiation of DNA synthesis in
renal epithelial cells in culture. These findings suggest that some
physiological effects of this adenine nucleotide could be mediated by
proteins specified by protooncogenes.
