Figure 1

Dickkopf-1 is a target of zoledronic acid and atorvastatin in breast cancer cells in vitro . (A) Results from a WNT PCR array define Dickkopf-1 (DKK-1) as a target of zoledronic acid. MDA-231 cells were treated with zoledronic acid (100 μM) for 24 hours and assessed by a WNT array. A heat map of all tested genes is shown on the right: green, increased expression compared with control; red, decreased expression compared with control; grey, nondetectable gene. All genes that were regulated at least twofold are separately depicted on the left. (B) Basal expression of DKK-1 in different breast cancer cell lines assessed by polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA) and western Blot. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a loading control. (C), (D) Suppression of DKK-1 by zoledronic acid (ZOL; 100 μM) and atorvastatin (ATO; 10 μM) after 24 hours of exposure was confirmed in multiple cell lines. Assessment of unfarnesylated RAS (upper band) and ungeranylated RAP1A confirmed mevalonate pathway inhibition. Representative blots are shown. GAPDH is used as a loading control. Data for PCR and ELISA are shown as mean ± standard deviation of three independent experiments. *P < 0.05; **P < 0.01; ***P < 0.001.