DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer

The gene deleted in malignant brain tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor for brain, gastrointestinal, and lung cancer. I t codes for a protein of unknown function belonging to the superfamily of s cavenger receptor cysteine-rich proteins. We aimed at getting insights into the functions of DMBT1 by expression analyses and studies with a monoclona l antibody against the protein. The DMBT1 mRNA is expressed throughout the immune system, and Western blot studies demonstrated that isoforms of DMBT1 are identical to the collectin-binding protein gp-340, a glycoprotein that is involved in the respiratory. immune defense. Immunohistochemical analys es revealed that DMBT1 is produced by both tumor-associated macrophages and turner cells and that it is deregulated in glioblastoma multiforme in comp arison to normal brain tissue. Our data further suggest that the proteins C RP-ductin and bensin, both of which hare been implicated in epithelial diff erentiation, are the DMBT1 orthologs in mice and rabbits, respectively.. Th ese findings and the spatial and temporal distribution of DMBT1 in fetal an d adult epithelia suggest that DMBT1 further plays a role in epithelial dev elopment. Rearrangements of DMBT1 vi ere found in 16 of 18 tumor cell lines , and hemizygous deletions were observed in a subset of normal individuals, indicating that the alterations in tumors may be a result of both pre-exis ting deletions uncovered by a loss of heterozygosity and secondary changes acquired during tumorigenesis. Thus, DMBT1 is a gene that is highly unstabl e in cancer and encodes for a protein with at least two different functions , one in the immune defense and a second one in epithelial differentiation.