Effects of c-erbB2 overexpression on the drug sensitivities of normal human mammary epithelial cells

Background: Overexpression of the gene c-erbB2, which encodes a receptor ty rosine kinase, in breast tumors has been linked with either increased or de creased response of breast cancer patients to various therapies. In breast cancer cell lines, overexpression of exogenous c-erbB2 sometimes alters dru g sensitivities but sometimes has no effect. To avoid the genetic complexit ies associated with established cancer cell lines, normal human mammary epi thelial cells (HMECs) were studied to determine whether c-erbB2 overexpress ion by itself would alter chemosensitivity. Methods: HMECs were designed to overexpress c-erbB2, and these cells were then evaluated for alterations i n chemosensitivity. Results: HMECs overexpressing c-erbB2 failed to show an y alterations in chemosensitivity to a panel of chemotherapeutic agents, as indicated by 95% confidence intervals on growth curves of cells treated wi th or without the agent of interest, With the use of fluorescence-activated cell sorting to enrich for HMECs overexpressing c-erbB2 on their surface, an 85% pure population of cells was isolated and their chemosensitivity was evaluated. Again, the cells failed to display any alterations in chemosens itivity. Conclusions: These results suggest that overexpression of c-erbB2 is not sufficient by itself to induce changes in chemosensitivity. Cellular studies using normal human cells in which the complexity of the system can be carefully controlled by the addition of one, two, or even more genes as sociated with cancer development may provide valuable information about how the products of the genes interact with each other and which combinations are critical in regulating chemosensitivity.