The Role of Growth-Regulated Oncogene (GRO) Proteins in Human Breast Cancer Growth
Annual rept. 15 May 2000-14 May 2001
CONNECTICUT UNIV HEALTH CENTER FARMINGTON
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This year 01 annual report describes the study, to date, on the role of the cytokine Growth-Regulated Oncogene GRO protein in human breast cancer. 1 the establishment of a tumor bank, 2 Immunohistochemical analysis showing the expression of GRO and its receptor, CXC-R2 in human breast cancer patient samples, 3 Quantitation of GRO levels in human breast cancer tissue sample homogenates and correlation of these levels with the expression of nine other cytokines and cytokine receptors as well as the levels of the estrogenprogesterone receptor expression, and 4 using human mammary epithelial and tumor cell lines we described the constitutive and inducible expression of not only GRO, but the closely related cytokine IL8. 1 GRO is expressed by breast cancer tumor cell and its receptor is expressed not only on tumor cells themselves, but also on vascular endothelial cells. This suggests that GRO may be involved in cancer cell proliferation and may be important in promoting vascularization by vascular endothelial cell activation. 2 Analysis of breast cancer tissue homogenates shows a significant correlation with the closely related cytokine, ILS. Furthermore, GRO expression correlates with the GROILS inducer IL-1 and the IL-1 Receptor 1. This suggests that tumor derived GRO and IL8 may result from tumor cell activation by IL-1. Additionally, GRO expression is inversely correlated to estrogen receptor expression, suggesting GRO expression is related to an unfavorable breast cancer patient disease outcome. 3 Our cell culture experiments support the data form the patient tumor samples showing IL-1 is a potent inducer of both GRO and IL8. These data clearly demonstrate the importance of the relationship between GRO and IL8, but more importantly, demonstrates the inductive ability of IL-1 to regulated expression og GRO and IL8.
- Medicine and Medical Research