Expression of MMPs and TIMPs genes in human breast cancer epithelial cells depends on cell culture conditions and is associated with their invasive potential.

Growth and invasiveness of breast cancer cells in adjacent and distant sites is associated with the expression of metalloproteinases (MMPs), which are capable of degrading almost all extracellular matrix macromolecules of supporting stroma. In order to identify markers useful for monitoring breast cancer pathogenesis and metastatic potential, we examined the expression of mRNAs encoded for MMPs and their endogenous inhibitors (TIMPs) in a panel of four epithelial breast cancer cell lines of high (MDA-MB-231 and ZR-75-1) and low (MCF-7 and BT-20) metastatic potential, and their expression was compared with that of normal mammary cells (MCF-12A). Expression patterns were evaluated using cell cultures in serum-containing and serum-free media. Gene expression studies were performed following cell cultures, RNA isolation, reversed transcription and polymerase chain reaction. Both normal and breast cancer cells express MMPs and TIMPs at various levels, depending on cell type and culture conditions. Comparison of their mRNA levels from serum-containing media showed that MMP-9, MT2-MMP and TIMP-1 are highly expressed in all cancer cells as compared to normal ones, whereas MMP-1 and -7 are overexpressed only in breast cancer cells of high invasion potential. In serum-free cultures, the highly metastatic cells retain the overexpression profile for MMP-1 and -7. Furthermore, MT2-MMP and TIMP-1 were constitutively expressed and they can also be correlated with cancer cells, whereas constitutive expression of MMP-9 was similar in normal and cancer cells. The results of this study indicate that the expression of MMPs is dependent on the culture conditions, i.e. the growth factors present in serum-containing media. Furthermore, data suggest that, independently of cell culture conditions, the expression of MT2-MMP may be associated with malignant transformation of mammary cells and the overexpression of MMP-1 and -7 with the highly metastatic potential of epithelial breast cancer cells.