The Role of the Suppressor, Rsu-1, in Regulation of Ras Signal Transduction in Breast Cancer Cells.
Annual rept. 2 Jun 97-1 Jun 98
HENRY M JACKSON FOUNDATION ROCKVILLE MD
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Epidermal growth factor EGF family of ligands bind to a number of related receptors and stimulate mitogenesis in mammary cells. Signal transduction downstream of the EGF family of receptors involves activation of the GTPase Ras and its effectors. RSU-1, a cDNA identified as an inhibitor of Ras-induced transformation, was HA-epitope tagged and introduced into expression vectors. The HA-RSU-1 vectors were transfected into MCF7 and MCFlOA cell lines. Transfectants were selected and tested for response to EGF and serum stimulation. Analysis of the several kinase pathways which have been characterized as dependent on Ras activation were tested in the RSU- 1transfectants following stimulation of serum starved cells with EGF or serum. Expression of HA-Rsu- 1 resulted in resulted in an increase in activation of Erk-2 kinase and a decrease in activation of p54 Jun kinase. Activation of AKT kinase by serum was unaffected by Rsu-1 expression. These results demonstrate that Rsu-1 can alter signal transduction downstream of Ras in MCF7 cell line. HA-Rsu-1 transfectants had similar anchorage dependent growth rates as the control cell lines, but exhibited a reduction in anchorage independent growth.
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