Receptor tyrosine kinases (RTKs) convey pro-tumorigenic responses in breast, colon, lung, and prostate cancer. RTKs including IGF-IR, EGFR, and Met, propagate tumor behavior by increasing cell proliferation, tumor cell movement (motility), tissue invasion, and metastasis. We focus on a group of proteins known as JNK (c-Jun N-terminal Kinases) which are activated by receptor tyrosine kinases in breast cancer models. Three jnk genes are expressed in eukaryotes and their products were initially thought to convey cell death signals. However, our studies have shown that jnk1 and jnk2 gene products have diverse roles. To better understand their various functions, we study jnk1 and jnk2 in mammary gland development, mammary tumorigenesis/metastases, and response to chemotherapy treatment. We have found that in response to activation of RTKs, JNKs play critical roles in tumorigenesis, DNA damage, cell migration, and metastasis. JNKs also affect mammary development by influencing mammary cell differentiation. Using microarray technology we have identified several genes through which JNKs influence cellular response to growth factors. Our current studies are aimed to better characterize how JNKs mediate these phenotypic responses. Ultimately, we hope to evaluate if JNK can be therapeutically targeted to treat breast cancer patients.