Abstract

Abstract Introduction: Leptin is a multifunctional hormone produced by adipocytes. It plays important role in angiogenesis. Induction of cell proliferation, survival and anchorage-independent growth. These leptin activities are mediated through leptin receptor (ObR) that binds leptin molecule and stimulates Jak/STAT 3, ERK ½, cyclin D1 expression and other signal pathways. A recent data show that targeting leptin signaling may reduce mammary carcinogenesis and breast cancer (BC) progression. However, the link between obesity and leptin expression in serum/breast tumor as well as its role in modulation of estrogen receptors (EsR) and HER2/neu expression is not clear. Material and methods: We studied leptin, ObR, EsR, HER2/neu expression in patients with sporadic, familial and pregnancy-associated BC by RT PCR using BC fresh tissue and primers for genes encoding leptin, ObR, EsR-α, β. Leptin level in the patient sera was estimated also by ELISA (Leptin Sandwich DRG, DRG Diagnostics, Germany) followed by comassie staining. The data on immunohistochemical staining of HER2/neu, EsR and PrR were also obtained. In control group were patients with benign fibroadenoma (BFa) and healthy women of comparable age. Results: RT PCR results and immunohistochemistry method are mainly concordant : only 5% (5/29) of data were different. In triplonegative tumors (n=40) leptin overexpression was significantly higher than in other tumor types. Blood sera leptin level was correlates positively with ObR expression. Leptin expression in tumor tissue also correlates with HER2/neu over expression in all BC groups except triplonegative ones: Esr (-), PrR(-), HER2/neu(-). Serum leptin levels in BFa patients was higher (100-300 ng/ml) than in healthy women and the mean leptin level in BC patient of comparable age and body weight. Moreover, leptin serum level was positively correlates with ObR expression in tumors on I-III BC stages and with high body weight index (obesity). Conclusions: The data obtained indicate that leptin/ObR maight involved in BC progression. It indicates that ObR suppression isthe possible way for target BC therapy, especially of triplonegative tumors which do not express HER2/neu, so hormone therapy is not effective for these neoplasia. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-08-09.

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