Lysyl oxidase propeptide inhibits FGF induced ras signaling in prostate cancer cells

BIOL 59

Amitha H. Palamakumbura, amithahp@bu.edu1, Siddharth R. Vora, vora@bu.edu1, Gail E. Sonenshein, gsonensh@bu.edu2, and Philip C. Trackman, trackman@bu.edu1. (1) Division of Oral Biology, Boston University Goldman School of Dental Medicine, 700 Albany Street, W210, Boston, MA 02118, (2) Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118
Lysyl oxidase (LO) was found to inhibit the transforming activity of the ras-oncogene in fibroblasts. LO is secreted as a 50-kDa inactive proenzyme (Pro-LO) and cleaved to a functional 30-kDa enzyme and an 18-kDa pro-peptide (LOPP). We have recently shown that the LOPP domain, and not the 30-kDa enzyme, inhibits the ras-transformed phenotype in fibroblasts. Here we report that the LOPP inhibits the ras dependent MEK/Erk and PI3K/Akt pathways and the cell cycle progression in androgen independent prostate cancer cell lines, DU145 and PC-3. Real time qPCR analysis revealed a reduced LO expression in these cell lines. Furthermore, LOPP reduced the FGF-2 induced Erk phosphorylation suggesting the involvement of FGF signaling intermediates upstream of ras in this mechanism. Identifying these molecular targets may permit the design of novel therapeutic drugs against prostate cancer. Supported by NIH grants CA82742, DE14066.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007