PRODUCTION AND REGULATION OF INTERLEUKIN-11 BY BREAST-CANCER CELLS

We have studied the production of interleukin-11 (Il-11) in 13 breast cancer cell (BCC) lines. Two of these cell lines (MDA-MB-231 and Hs578 T) expressed the cytokine at both the protein and mRNA levels. Ii-II d id not modulate the growth of five BCC lines examined, including the t wo cytokine-producing BCC lines. The production of Ii-Il was increased by transforming growth factor-pi in a dose-dependent manner with a ra pid (2 h) and transient (24 h) mRNA induction, but not by epidermal gr owth factor, insulin-like growth factor-I and -II, basic fibroblast gr owth factor, platelet-derived growth factor or parathyroid hormone. Th e cyclic AMP inducer, forskolin, and the activator of protein kinase C , phorbol 12-myristate 13-acetate, also stimulated the production of I l-11. Besides Ii-II, MDA-MB-231 and Hs578T were the only BCC lines to produce interleukin-6 (Il-6) protein and mRNA. Since Ii-Il and Il-6 ar e potent stimulators of osteoclast development and bone is a major sou rce of TGF-beta(1), our data suggest that Ii-Il, together with Il-6, c ontributes to the high bone destructive capacity of MDA-MB-231 cells a nd could play a role in breast cancer-induced osteolysis. Published by Elsevier Science Ireland Ltd.