Induction of Transforming Growth Factor α Expression in Mouse Mammary Epithelial Cells after Transformation with a Point-Mutated c-Ha-ras Protooncogene

NOG-8 ras cells are a normal mouse mammary epithelial cell line transfected with a plasmid containing a glucocorticoid-inducible mouse mammary tumor virus long terminal repeat linked to the activated c-Ha-ras protooncogene. After addition of dexamethasone, there is a rapid induction (within 1–3 h) of p21ras protein that is concomitant with a parallel induction of the c-Ha-ras specific mRNA. After 4–6 days of dexamethasone treatment, NOG-8 ras cells are able to grow as colonies in semisolid medium. Between 9 and 12 days of dexamethasone treatment, there is a 5- to 6-fold increase of transforming growth factor α (TGFα) activity in the conditioned medium from NOG-8 ras cells. A 60–65% reduction in epidermal growth factor cell surface receptors on NOG-8 ras cells also occurs during this time interval. A 3- to 4-fold increase of the expression of a specific TGFα mRNA can be detected within 2 days of dexamethasone treatment, preceding the increase in TGFα protein found in the conditioned medium. Exogenous TGFα ...