Induction of KAI-1 expression in metastatic cancer cells by phorbol esters

KAI-1 is a tumor suppressor gene whose down-regulation has been shown to be associated with the development of metastases of cancer cells. Here, we demonstrated that KAI-1 expression was induced by activating protein kinase C even in metastatic prostate cancer cell lines in which its expression was significantly down-regulated. KAI-1 expression was enhanced in a dose-dependent manner by PMA, and its induction is at least in part due to transcriptional activation. Pretreatment with calphostin C abrogated its induction by PMA. Our findings may provide useful information for developing a novel drug capable of inducing KAI-1 expression and thereby inhibiting metastasis.