Estrogen receptor-alpha and C-ERBB-4 expression in breast carcinomas

The presence of estrogen receptors (ERs) in breast carcinomas is important for clinical response to endocrine therapy. However, the cellular mechanism s following ER activation are not fully understood. It has been indicated t hat expression of the ER is associated with the expression of c-erbB-4. To address this question, 103 breast carcinoma samples were studied using reve rse transcriptase polymerase chain reaction (RT-PCR) analysis after applica tion of a microselection method for RNA isolation. Total RNA for RT-PCR was isolated from 20-mum-thick frozen sections. which were made from microsele cted areas. Paraffin blocks from 98 of these 103 tumors were also immunohis tochemically examined. Significant associations between ER-alpha. and c-erb B-4 mRNA and protein expressions were found in the present study with both methods. One-fourth of the tumors did not express ER-alpha. (22%, 24%, and 26% with chemical binding, immunohistochemistry, and RT-PCR, respectively). About one-half of the ER-alpha negative tumors did not express c-erbB-4 on both mRNA and protein levels (48% with RT-PCR and 46% with immunohistochem istry, P=0.001 for both methods). The endocrine therapy responsive breast c ancer cell lines MCF-7 and T47-D were positive for both ER-alpha and c-erbB -4 expression, while the endocrine therapy nonresponsive breast cancer cell lines MDA-MD-231 and SK-BR-3 were not. Thus, we confirm the association be tween the expression of ER-alpha and c-erbB-4 mRNA and protein in breast ca rcinomas, indicating a role for c-erbB-4 in estrogen signal transduction.