Breast cancer is the second leading cause of cancer related deaths in women. The outcome of cancer treatment using chemotherapeutic drugs depends on the sensitivity of cancer cells to drugs. Cancer cells which are not sensitive to drug treatment will not be killed. 30% of breast cancer cells show increased expression of the erbB2 oncogene, a Type I receptor gene. This over-expression is observed in all stages of the breast cancer and is found at metastatic sites as well as the primary tumor. A positive correlation between erbB2 levels and sensitivity to some drugs has been well documented in the literature.

The ability of malignant cells to develop resistance to a range of structurally and functionally unrelated antineoplastic drugs is called multidrug resistance (MDR). My analysis of sensitive (MCF-7) and multidrug resistant (MCF-7/ADR) breast cancer cell lines shows lower levels of erbB2 in the MCF-7/ADR resistant cells as compared to the MCF-7 cells. Constitutive levels of raf-1 and MAP kinase, two proteins in the same intracellular signaling pathway, were also lower in MCF-7/ADR cells as compared to sensitive cells. Although expression of c-fos, which is activated by the MAP kinase cascade, was lower in the resistant cells, the expression of c-jun, which is activated by the jun kinase signaling cascade, was higher. This suggests that different signaling pathways are predominant in sensitive and resistant cells. Based on these results, we hypothesize that the balance of signaling through the MAP kinase and jun kinase cascades by Type I receptors is crucial for sensitivity to chemotherapeutic drugs.

In support of my hypothesis, my studies found that c-erbB2 transfected MCF-7 cells, having the highest levels of erbB2, had increased basal levels of MAP kinase, and these transfected cells were more sensitive to adriamycin drug treatment than sensitive MCF-7 cells. Investigating the role of the Type I receptors to elicit a response of breast cancer cells to chemotherapy treatment may help in the design of better regimes for treating patients with breast cancer.