EPIDERMAL GROWTH-FACTOR RECEPTOR LEVELS INCREASE BUT EPIDERMAL GROWTH-FACTOR RECEPTOR-LIGAND LEVELS DECREASE IN MOUSE MAMMARY-TUMORS DURINGPROGRESSION FROM HORMONE DEPENDENCE TO HORMONE INDEPENDENCE

Twenty-six serially transplanted Grunder (GR) strain mouse mammary tum ors were analyzed for epidermal growth factor receptor (EGFR) and EGFR -ligand levels, in addition to steroid hormone receptors (estrogen rec eptor, ER, progesterone receptor, PgR). In concordance with earlier st udies, hormone dependent (HD) and hormone responsive (HR) tumors were found to be positive for both ER and PgR, whereas hormone independent (HI) tumors contained only 30% of the ER concentration that was found in the HD tumors. PgR was undetectable in HI tumors. HI tumors contain ed 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an observation which shows remarkable concordance with studies on EGFR in human breas t cancer. On the other hand, the level of EGFR-ligand(s) was positivel y associated with ER levels and was three-fold higher in HD/HR tumors than in HI tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of downregulation by EGFR ligands produced under ER control. During progression to hormone independence this downregulatio n of EGFR is then abolished in absence of ER. The increase in EGFR may therefore be a secondary effect rather than a key event in the progre ssion to hormone independence in this mouse mammary tumor model.