Surface expression of erbB-2 protein is post-transcriptionally regulated in mammary epithelial cells by epidermal growth factor and by the culture density.

The control of expression of the erbB-2 protein was examined in two mammary epithelial cells lines, HC11 and 31E. The erbB-2 protein content varied dramatically depending upon cell density and upon the presence of epidermal growth factor (EGF) in the culture medium. The changes in protein content were not due to variation in the erbB-2 mRNA level. Analysis of the metabolic turnover of the erbB-2 protein showed that its rate of degradation was two- to threefold higher in cells growing at low density than in cells confluent for 2 days. The addition of EGF to the culture medium caused an increase in the phosphoamino acid content and an increase in the turnover of the erbB-2 protein. Cell fractionation experiments were performed, and a shift in the cellular localization of the erbB-2 protein towards the lysosomal compartment in EGF-treated HC11 cells was found. This is reflected by an increase in the degradation rate of the erbB-2 protein. These findings suggest that in mammary epithelial cells the stability of the erbB-2 protein is an important regulatory control point in determining the level of the protein. The degradation rate is sensitive to cell confluency and is controlled by EGF receptor activity.