Expression of P185erbB-2, P160erbB-3, P180erbB-4, and heregulin alpha in human normal bronchial epithelial and lung cancer cell lines

The receptors erbB-3 and erbB-4 are members of the type 1 tyrosine kinase r eceptor family which also comprises epidermal growth factor receptor (EGF-R ) and erbB-2. ErbB-3 and erbB-4 receptors are known to bind a family of rel ated proteins termed heregulins. In this study, we report differential expr ession of P185erbB-2, P160erbB-3 and P180erbB-4, and their ligand heregulin alpha, in normal bronchial epithelial, and non-small cell lung carcinoma ( NSCLC) cell lines. Expression of P185erbB-2 and P160erbB-3 vary from very l ow to a high level in NSCLC cell lines and a low level in normal bronchial cells. In contrast, P180erbB-4 was detected only in NSCLC cell lines but no t in normal bronchial cells. Heregulin alpha is expressed at intermediate l evels in the normal and cancer cell lines studied Immunoprecipitation, usin g antibodies to erbB-2, erbB-3 or erbB-4 receptors, coupled to phosphotyros ine Western blot analysis indicates that these three receptors are constitu tively tyrosine phosphorylated in lung cancer cell lines, but only erbB-2 a nd erbB-3 are autophosphorylated in normal cells. These data suggest that c onstitutive activation of erbB-2 erbB-3 and erbB-4 receptors could be induc ed by heregulin a via an autocrine loop mechanism, and that the active form s of erbB-4 may cooperate with the other members of the EGF-receptor family in human lung carcinogenesis.