EXPRESSION AND FUNCTION OF MEMBERS OF THE CYTOKINE RECEPTOR SUPERFAMILY ON BREAST-CANCER CELLS

Receptors for the cytokines leukemia inhibitory factor (LIF), interleu kin-6 (IL-6), oncostatin M (OSM), ciliary neurotrophic factor (CNTF) a nd interleukin-11 (IL-11) are members of the structurally conserved he mopoietin receptor superfamily, In addition, they all share the transm embrane signalling protein gp130, In this paper the expression and fun ction of this family of receptors in breast cancer cells was examined, RT-PCR analyses demonstrated that gp130 was expressed in 12/12 breast cell lines and the specific receptor alpha-chains for IL-6, LIF, IL-1 1 and CNTF were expressed in the majority of these cell lines, This wa s in contrast to other hemopoitin receptors, Examination of 50 clinica l samples of malignant breast tissue by RT-PCR showed a similar patter n of expression of gp130 associated receptors, Treatment of breast can cer cell lines with OSM resulted in changes in cellular morphology. Ce llular proliferation was inhibited following exposure to OSM (3/4 cell lines), IL-11 (2/4 cell lines), and by IL-6 and LIF (1/4 cell lines), Cell surface binding of LIF and OSM was also documented, The expressi on of these receptors in 12/12 cell lines and greater than 95% of clin ical samples suggests that these molecules may be important in regulat ing the growth of breast cells.