Cathepsin D, IGF-II and EFABP promotes breast cancer progression in African Amer.

Loma Linda University, Loma Linda CA

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Abstract

The disparity in survival among African American (AA) women affected by breast cancer is associated with[unreadable] poorly known clinical and pathological characteristics. A comprehensive molecular approach to understand[unreadable] the biological basis related to the increased mortality and poorer prognosis in this ethnic group is needed to[unreadable] eliminate differences in outcomes among AA patients. We propose to address this need by demonstrating[unreadable] that IGF-II, EFABP and cathepsin D (CD) are associated with the disparity observed in AA breast cancer[unreadable] patients outcome. The hypothesis underlying this proposal is that increased IGF-II and cathepsin D caused[unreadable] by oxidative stress and lack of EFABP promotes rapid tumor growth and metastasis resulting in a survival[unreadable] disparity. The specific aims of the proposal are: 1) Demonstrate that higher levels of CD and IGF-II are[unreadable] present in normal and breast tumor tissues of AA patients as compared to tissues from Caucasian patients;[unreadable] 2. Demonstrate that CD and IGF-II are highly expressed in breast cancer cells established from AA patients[unreadable] in vitro and that increase in these proteins promotes rapid tumor growth and metastasis in an animal model[unreadable] in vivo; 3. Demonstrate that the expression of EFABP is reduced in normal tissues from AA breast cancer[unreadable] patients as compared to tissues from Caucasian patients.Our purpose is to demonstrate that higher levels of[unreadable] IGF-II and cathepsin D are present in paired tissues from AA breast cancer patients and that their expression[unreadable] correlates with decreased survival. We will further test our hypothesis in vitro and in vivo. Analysis in vitro of[unreadable] the breast cancer cells established from AA patients will allow us to identify the specific forms of IGF-II and[unreadable] CD secreted by these cells as compared to forms secreted from cells from Caucasian patients. Higher[unreadable] molecular forms of IGF-II and CD are associated with glycosylation and are more potent in promoting tumor[unreadable] progression. The in vivo animal model will allow us to characterize the progression of the disease.[unreadable] Correlation of CD, IGF-II and EFABP with disease progression will provide much needed insight in[unreadable] understanding the mechanisms of how differential expression of these factors may account for the disparity[unreadable] in survival outcomes observed in AA breast cancer patients. The technical objectives, research design, and[unreadable] methods for this proposal will confirm, expand, and extend these preliminary findings. The hypothesis will be[unreadable] supported if these technical objectives are achieved.