University of Florida College of Medicine
Amount Funded: $90,000 (2008-2009) $90,000 (2009-2010)
This proposal proposes to look at a gene called PRAME. The name is the equivalent of “preferentially expressed antigen in melanoma expression”. This gene has been associated with melanoma and some other hematopoietic cancers. The PRAME gene has also been associated with aggressive breast cancers. The PIs proposed to look at tumor cell lines that express the PRAME gene and to see exactly what mechanisms may make breast cancers more aggressive. Targeted therapies may then be used to interfere with the mechanisms that the PRAME gene may control. The PRAME gene may be predictive of a more aggressive cancer and has not been used up to this point in time as a clinical indicator of prognosis. We do use two tests currently in node negative hormone receptor positive patients: one test is called Ocotype DX. The second test is called MammoPrint. The PRAME gene may be another predictor of aggressiveness and need for additional therapy, i.e. chemotherapy. In addition, as I mentioned before, the PIs may be able to discover the mechanisms by which the PRAME gene influences aggressiveness of the cancer and may therefore, find mechanisms to interfere with those processes.
Florida State University
Qing-Xiang (Amy) Sang
"Interactive role of Stroma in Breast Cancer"
This is an interesting proposal looking at the stroma around a breast cancer or in which a breast cancer may grow. This interesting concept has evolved over the last several years. The PIs allude to the point that many authors have that the stroma, that is, the matrix that the tumor grows in, may in fact be more important than was hitherto thought. The stroma may secrete proteins that actually cause a normal breast cell to change into a malignant cell, or that may influence a preinvasive cancer to change into an invasive cancer. We know that there are interactions between the tumor cell and the stroma, but what those interactions are and what came first, the chicken or the egg, is unknown. The PIs propose to look for differences in the stroma between and epithelial cells in a collection of breast tissues using genomic and proteomic approaches. It is an interesting concept that may clarify the role of stroma in breast cancer progression as well as identify novel biomarkers that will be an aid in diagnosing and predicting the evolution of ductal carcinoma in situ, one of the early forms of breast cancer.
H.Lee Moffitt Cancer Center & Research Institute
“CG/LH Receptor as a New Target”
Mechanisms that suppress apoptosis are suspected to contribute to the development of resistance to anti-cancer drugs and may prevent complete responses to neoadjuvant chemotherapy. A hormone that could be useful in the induction of apoptosis in breast cancer cells is human chronic gonadotropin (hCG). Most hCG actions are mediated by a receptor, which also binds luteinizing hormone (LH). CG/LH receptors have been detected in normal breast epithelial cells, breast cancer tissues, and breast cancer cell lines suggesting a role of this receptor in breast tissue. Several studies have reported that full-term pregnancy at a young age has a protective effect against the development of breast cancer. The long-term objective of this research project is to characterize the exact mechanism(s) involved in the hCG-dependent induction of apoptosis in breast cancer. In this research proposal the long-term objective will be reached through the following specific aims: Aim I: To determine the mechanisms of apoptotic induction by hCG in breast cancer cells; and Aim II: To examine whether the expression levels of CG/LH receptors could predict response to hCG treatment. Studies will also investigate whether major prognostic indicators in breast cancer (i.e., HER2, estrogen receptor) could influence the function/expression of the CG/LH receptor.
University of Miami-SCCC
Amount Funded: $5,000