In vivo effect of an luteinizing hormone-releasing hormone analog on vascular endothelial growth factor and epidermal growth factor receptor expression in mammary tumors

Background: The hypothalamic luteinizing hormone-releasing hormone (LHRH) is well known for its role in the control of pituitary gonadotropin secretion and it has demonstrated a direct antiproliferative effect on some cancer cell lines of LHRH and its synthetic analogs. The study was designed to assess whether administration of the LHRH analog (goserelin) has any effect on the expression of the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) in rats with N-nitroso-N-methylurea (NMU)-induced-mammary tumors " in vivo". Materials and Methods: The animals with tumors were assessed after acute or chronic treatment with goserelin, and in all the animals VEGF and EGFR expression was examined both in plasma and tumor homogenates by enzyme immunoassay. Results: The basal plasma values of VEGF were lower in the healthy control group than in rats with NMU-induced tumors ( P = 0.025). Following acute treatment with goserelin, VEGF expression in plasma increased above basal levels after 60 min ( P = 0.05) and dropped during chronic treatment. Likewise, in the tumor homogenate the mean VEGF expression was higher at 60 min post-goserelin administration than the basal levels, although VEGF expression then diminished at 90 min. Plasma EGFR expression was higher in rats with NMU-induced tumors than in healthy controls ( P < 0.01). Conclusions: The results allow us to conclude that goserelin may exert a short-term stimulatory effect on the release of VEGF, as well as a long-term inhibitory effect on VEGF but not EGFR expression.