Of note, treatment with p38 inhibitors suppressed this increase in DKK-1 mRNA expression and p38 MAPK/HSP27 protein phosphorylation, supporting the distinct role of p38 MAPK signaling as anisomycin itself also induces the JNK/SAPK signaling pathway.46 As shown by Thudi et al.,47 the upregulation of DKK-1 in the osteoblastic prostate cancer cell line Ace-1 altered the osteoblastic phenotype toward an osteolytic phenotype in vivo. This highlights a key role of the levels of the Wnt inhibitor DKK-1 in regulating the osteoblastic/osteolytic appearance of prostate cancer bone metastases. This evidence concerns the gene DKK1 and Familial prostate cancer.