EXPRESSION OF THE ERBB-2 PROTOONCOGENE DURING DIFFERENTIATION OF THE MAMMARY-GLAND IN THE RAT

The erbB-2 proto-oncogene encodes a transmembrane protein (p185) that is a tyrosine kinase sharing high homology with the epidermal growth f actor receptor. Its expression in mammary cell lines is modulated by e strogens, epidermal growth factor, and several other factors at the RN A and/or protein levels. We have used in situ hybridization, immunoblo t, and immunohistochemistry to study the expression of erbB-2 in the r at mammary gland at various stages of differentiation. evbB-2 RNA is p resent at low levels in mammary glands from virgin, mid-pregnant, and lactating female rats. Increased RNA levels can be detected in early a nd late pregnancy. In all samples, erbB-2 RNA has been found in all ep ithelial cells. Immunohistochemistry with antisera directed against th e intracellular domain of p185 has shown that only a minority of cells are stained in virgin and early pregnant samples, whereas no staining is seen in late pregnant and lactating mammary glands. In contrast, i mmunoblot analysis has detected the highest levels of p185 in late pre gnancy and during lactation. This may reflect either that the cellular content of p185 is too low to be detected by immunohistochemistry, or that the epitopes are not accessible to the antisera in situ. Taken t ogether, our data indicate that erbB-2 is expressed by mammary epithel ial cells at all physiological stages and suggest that erbB-2 expressi on is modulated at both the RNA and protein level in vivo.