Crosstalk Between Leptin Receptor and IGF-IR in Breast Cancer: A Potential Mediator of Chemoresistance
Annual rept. 18 Feb 2009-19 Mar 2010
EMORY UNIV ATLANTA GA
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Obesity is a major risk factor for breast cancer, and is associated with reduced treatment response and reduced overall survival. The obesity-associated hormones IGF-I and leptin and their receptors, IGF-IR and leptin receptor Ob-R, are elevated in breast cancer. Previously we reported a novel interaction and cross-talk between IGF-IR and Ob-R in breast cancer cell lines. Our work this year has focused on determining the effects of combined inhibition of Ob-R and IGF-IR on breast cancer cell proliferation. Because we have been unable to identify an effective inhibitor of leptin receptor, we are using an inhibitor of JAK2, which is immediately downstream of the leptin receptor. Inhibition of JAK2 reduced MCF7 cell proliferation. Results described in this report indicate that adipocyte-secreted factors found in conditioned media collected from adipocytes may in fact alter response to taxanes. Furthermore, MCF7 cells appear to be dependent upon JAK2 signaling, which is downstream of leptin receptor and potentially upregulated during obesity. Thus, JAK2 inhibition downstream of leptin receptor is a potential strategy for combating obesity-associated breast cancer and possibly for improving chemosensitivity of obesity-associated breast cancers.
- Medicine and Medical Research