Role of Adrenomedullin in Breast Cancer Bone Metastasis and Chemoresistance
Annual summary 15 Apr 2006-14 Apr 2007
VIRGINIA UNIV CHARLOTTESVILLE
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The majority of patients with advanced breast cancer develop bone metastases, which are incurable. Recently, tumor-secreted factors have shown promise as targets for the treatment of bone metastasis. Adrenomedullin AM is a breast cancer-secreted peptide that is pro-proliferative, anti-apoptotic, pro-angiogenic, and stimulates new bone formation. AM overexpression increases bone metastases while AM knockdown decreases bone metastases in mouse models of prostate and lung cancer respectively. ObjectiveHypothesis The objective of this project is to validate AM as an important target for the treatment of breast cancer bone metastasis. I hypothesize that AM expression increases bone metastases and resistance to chemotherapy. Specific Aims 1 To determine if AM expression by breast cancer cells increases bone lesion formation in bone metastasis mouse models. 2 To determine the role of AM in breast cancer cells. Key Research Accomplishments 1 A human AM expression vector has been produced and is being used to make stable MCF-7 AM-overexpressing cells. 2 Stable AM shRNA knockdown MDA-MB-231 breast cancer cell clones have been produced and will be ready for mouse heart injection in June. 3 Current evidence does not indicate that AM is regulated by RhoGDl2 in breast cancer cells. Relevance Currently no treatments improve overall survival for breast cancer bone metastasis patients. Studying AM may lead to the development of an adjuvant therapy to improve treatment.
- Medicine and Medical Research