Connective tissue growth factor induces apoptosis in human breast cancer cell line MCF-7

Connective tissue growth factor (CTGF) is a member of an emerging CCN gene family that is implicated in various diseases associated with fibro-prolife rative disorder including scleroderma and atherosclerosis. The function of CTGF in human cancer is largely unknown. We now show that CTGF induces apop tosis in the human breast cancer cell line MCF-7. CTGF mRNA was completely absent in MCF-7 but strongly induced by treatment with transforming growth factor beta (TGF-beta). TGF-beta by itself induced apoptosis in MCF-7, and this effect was reversed by co-treatment with CTGF antisense oligonucleotid e. Overexpression of CTGF gene in transiently transfected MCF-7 cells signi ficantly augmented apoptosis. Moreover, recombinant CTGF protein significan tly enhanced apoptosis in MCF-7 cells as evaluated by DNA fragmentation, Td t-mediated dUTP biotin nick end-labeling staining, flow cytometry analysis, and nuclear staining using Hoechst 33258. Finally, recombinant CTGF showed no effect on Bar protein expression but significantly reduced Bcl2 protein expression. Taken together, these results suggest that CTGF is a major ind ucer of apoptosis in the human breast cancer cell line MCF-7 and that TGF-b eta-induced apoptosis in MCF-7 cells is mediated, in part, by CTGF.