BNF-1, a novel gene encoding a putative extracellular matrix protein, is overexpressed in tumor tissues

In an effort to identify novel genes relevant to tumor angiogenesis, we compared the genes expressed in a matched pair composed of vascularized breast tumor and its adjacent normal tissue obtained from the same cancer patient. Using differential display, we identified a cDNA fragment that was reproducibly upregulated in vascularized breast tumor. Up-regulation of this gene fragment in vascularized breast tumor was further verified by semi-quantitative PCR on the same RNA pair using gene-specific primers. The cDNA encoding the full-length ORF of that gene was then cloned by both 3' and 5' RACE. Sequence analysis showed that this gene encodes an ORF of 1353 bp having a hydrophobic N-terminal signal sequence and a cleavage site. We named this novel gene BNF-1 (breast tumor novel factor 1). The mature protein of this gene contains cysteine-rich repeats that are a specific feature of several extracellular matrix proteins including thrombospondin-1, thrombospondin-2, pro-collagen type 1, and von Willebrand Factor 1. PCR analysis of BNF-1 expression in a variety of human adult normal tissues revealed that BNF-1 is expressed predominantly in liver, heart, prostate, testis, and ovary. To further study the expression pattern of this novel gene in tumor tissues, we extended our analysis to additional matched pairs of tumor tissues obtained from breast, lung, and colon cancer patients. We show here that BNF-1 is over-expressed not only in breast tumors but also in lung and colon tumors.