MIDKINE INDUCES THE TRANSFORMATION OF NIH3T3 CELLS

Midkine (MK) is a heparin-binding growth factor and is frequently expr essed at high levels in many human carcinomas. To investigate further the roles of MK in the regulation of cell growth, we introduced MK exp ression in NIH3T3 cells. A mixture of transfectants of an MK expressio n vector, but not a control vector, formed colonies in soft agar, show ed an elevated cell number at confluence, and formed tumours in nude m ice. An interesting characteristic of the transformed cells was that t hey became spontaneously detached from the culture dish substratum. In the transformed cells, MK was not only secreted, but also localized, in the perinuclear region as spots. The present data indicate that MK has the potential to transform NIH3T3 cells and suggest that overexpre ssion of the MK gene may promote unregulated cell growth in vivo.