Luteinizing hormone-releasing hormone (
LHRH or
GnRH) is not only produced by hypothalamus, but also by other normal and
cancer tissues.
GnRH peptide agonists and antagonists inhibit the proliferation of
breast cancer cells, but their effect on the expression of
metalloproteinases (
MMPs) and their tissue inhibitors (TIMPs) has not been studied despite the fact that growth and invasiveness of
breast cancer cells in adjacent and distant sites is associated with the expression of
MMPs. In the present study, the effects of [D-Leu6, desGly10]
GnRH-NHEt (commercially available) and [D-Tic3, Deg6, desGlyl0]
GnRH-NHEt on gene expression of
MMPs and TIMPs in the
breast cancer cell line MCF-7 were examined with semi-quantitative RT-PCR. Results showed that incubation of MCF-7 cells with 30 microM of the synthetic
GnRH analogues for 48 h in serum-containing medium resulted in a decrease of MMP-9 expression and increase in MT1- and
MT2-MMP mRNA levels. Furthermore, both synthetic analogues induced a significant decrease in
TIMP-1 and
TIMP-3 mRNA levels and increase in
TIMP-2 mRNA levels. The impact of the observed changes on the expression of
MMPs and TIMPs warrants further investigation on the effects of
GnRH analogues on the invasiveness and metastatic potential of
breast cancer cells.