The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer

FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays.High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer.The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3), encoded by different genes, comprise an ancient family of single-strand DNA-binding proteins which have different functions in gene regulation. Though the FBP1, FBP2, and FBP3 genes are located on different chromosomes in mice as well as in humans, their primary sequences are highly related [1-3]. The genes encoding FBP1 and FBP3 are located on chromosomes 1p31.1 and 9q34.11, respectively. FBP1 (FBP) is designated the family progenitor. Besides regulating the transcription of the c-myc proto-oncogene [4-6], the FBP family has been shown to bind a variety of RNAs, therefore, FBPs are likely to be multifunctional.The far upstream element (FUSE) of the human c-myc proto-oncogene stimulates expression of c-myc in undifferentiated cells. FBP1, FBP2, and FBP3 are single-strand DNA-binding proteins that recognize FUSE. They posses all features of conventional transcription factors. The FBPs each bind sequence-specifically to o