DMBT1 Research Articles

Pre-Treatment of Swine Oviductal Epithelial Cells with Progesterone Increases the Sperm Fertilizing Ability in an IVF Model.

Simple SummaryThe involvement of the oviductal epithelial cells and progesterone hormone on the sperm fertilizing ability was investigated here by using an in vitro fertilization (IVF) swine model. By using different techniques, we demonstrated that oviductal epithelial cells (OECs) pre-treated with progesterone (P4) at 100 ng/mL represent the ideal environment for sperm capacitation, inducing a positive effect on the sperm acquisition of the fertilizing ability. Moreover, treatment of OECs with P4 modifies OVGP1, SPP1 and DMBT1 gene transcription but does not interfere with important cytoskeleton structures or cell doubling time, thereby allowing the correct development and progression of important biochemical pathways and signal transduction processes.Mammalian spermatozoa are infertile immediately after ejaculation and need to undergo a functional modification, called capacitation, in order to acquire their fertilizing ability. Since oviductal epithelial cells (SOECs) and progesterone (P4) are two major modulators of capacitation, here we investigated their impact on sperm functionality by using an IVF swine model. To that, we treated SOECs with P4 at 10, 100, and 1000 ng/mL before the coincubation with spermatozoa, thus finding that P4 at 100 ng/mL does not interfere with the cytoskeleton dynamics nor the cells’ doubling time, but it promotes the sperm capacitation by increasing the number of spermatozoa per polyspermic oocyte (p < 0.05). Moreover, we found that SOECs pre-treatment with P4 100 ng/mL is able to promote an increase in the sperm fertilizing ability, without needing the hormone addition at the time of fertilization. Our results are probably due to the downregulation in the expression of OVGP1, SPP1 and DMBT1 genes, confirming an increase in the dynamism of our system compared to the classic IVF protocols. The results obtained are intended to contribute to the development of more physiological and efficient IVF systems.

Balancing selection at the human salivary agglutinin gene (DMBT1) driven by host-microbe interactions

SummaryDiscovering loci under balancing selection in humans can identify loci with alleles that affect response to the environment and disease. Genome variation data have identified the 5′ region of the DMBT1 gene as undergoing balancing selection in humans. DMBT1 encodes the pattern-recognition glycoprotein DMBT1, also known as SALSA, gp340, or salivary agglutinin. DMBT1 binds to a variety of pathogens through a tandemly arranged scavenger receptor cysteine-rich (SRCR) domain, with the number of domains polymorphic in humans. We show that the signal of balancing selection is driven by one haplotype usually carrying a shorter SRCR repeat and another usually carrying a longer SRCR repeat. DMBT1 encoded by a shorter SRCR repeat allele does not bind a cariogenic and invasive Streptococcus mutans strain, in contrast to the long SRCR allele that shows binding. Our results suggest that balancing selection at DMBT1 is due to host-microbe interactions of encoded SRCR tandem repeat alleles.

Beneficial roles of probiotics on the modulation of gut microbiota and immune response in pigs.

The importance of probiotics in swine production is widely acknowledged as crucial. However, gaps still remain in the exact roles played by probiotics in modulation of gut microbiota and immune response. This study determined the roles of probiotic Lactobacillus plantarum strain JDFM LP11in gut microbiota modulation and immune response in weaned piglets. L. plantarum JDFM LP11 increased the population of lactic acid bacteria in feces and enhanced the development of villi in the small intestine. Metagenome analysis showed that microbial diversity and richness (Simpson, Shannon, ACE, Chao1) and the relative abundance of the Firmicutes were higher in weaned piglets fed probiotics. Five bacterial families were different in the relative abundance, especially; Prevotellaceae occupied the largest part of microbial community showed the most difference between two groups. Transcriptome analysis identified 25 differentially expressed genes using RNA-sequencing data of the ileum. Further gene ontology and immune DB analysis determined 8 genes associated with innate defense response and cytokine production. BPI, RSAD2, SLPI, LUM, OLFM4, DMBT1 and C6 genes were down-regulated by probiotic supplementation except PLA2G2A. PICRUSt analysis predicting functional profiling of microbial communities indicated branched amino acid biosynthesis and butyrate metabolism promoting gut development and health were increased by probiotics. Altogether, our data suggest that L. plantarum JDFM LP11 increases the diversity and richness in the microbial community, and attenuates the ileal immune gene expression towards gut inflammation, promoting intestinal development in weaned piglets.

A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle

BackgroundSurveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause.ResultsSeven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS.High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire.ConclusionsFDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given the phenotypic similarities in FDS affected calves, the genetic mapping and absence of further high impact variants in the critical genome regions, it is highly likely that the missense mutation in the FGFR2 gene caused the FDS phenotype in a dominant mode of inheritance.

Expression of the DMBT1 gene in breast cancer and its clinical significance

Objective To investigate the relationship between mRNA expression of DMBT1 in breast cancer tissues and clinicopathological characteristics of patients with breast cancer.Methods 60 cases of breast cancer tissues,30 cases of breast paracancerous hyperplasia tissues and 30 cases of breast paracancerous normal tissues were selected,then reverse transcription-polymerase chain reaction (RT-PCR) were performed to detect the differential expression of DMBT1 in mRNA levels.Furthermore,its relationship with clinicopathological characteristics of patients with breast cancer was analyzed.Results 44 out of 60 breast cancer tissues were detected no or low expression of DMBT1 (73.3％),and 16 out of 60 cases were found normal expression of DMBT1(26.7％).There were statistically significant differences between paracancerous normal tissues and breast cancer tissues,also between paracancerous hyperplasia tissues and breast cancer tissues (x2 =11.72,P =0.000 62 ; x2 =15.99,P =0.000 06).No significant difference was found between the low expression of DMBT1 with the age of patients (x2 =1.733,P =0.188),the size of tumor (x2 =0.776,P =0.378) and the histological grade of tissues (x2 =1.000,P =0.316).However,the loss rates of DMBT1 mRNA expression in patients with lymph node metastasis and clinical stage Ⅲ were higher than that in patients without metastasis and clinicalⅠ-Ⅱstage (x2 =4.885,P =0.026 ; x2 =4.600,P =0.032).Conclusion Low expression of DMBT1 mRNA is closely associated with the metastasis and clinical stage of breast cancer. Key words: Breast neoplasms; DMBT1 gene

Intestinal DMBT1 Expression Is Modulated by Crohn’s Disease-Associated IL23R Variants and by a DMBT1 Variant Which Influences Binding of the Transcription Factors CREB1 and ATF-2

ObjectivesDMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression.MethodsSeven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn’s disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays.ResultsIL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0×10−7, OR 1.42; 95% CI 1.24–1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1×10−18). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele.ConclusionWe identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.

Gene Polymorphisms in African Buffalo Associated with Susceptibility to Bovine Tuberculosis Infection

Bovine tuberculosis (BTB) is a chronic, highly infectious disease that affects humans, cattle and numerous species of wildlife. In developing countries such as South Africa, the existence of extensive wildlife-human-livestock interfaces poses a significant risk of Mycobacterium bovis transmission between these groups, and has far-reaching ecological, economic and public health impacts. The African buffalo (Syncerus caffer), acts as a maintenance host for Mycobacterium bovis, and maintains and transmits the disease within the buffalo and to other species. In this study we aimed to investigate genetic susceptibility of buffalo for Mycobacterium bovis infection. Samples from 868 African buffalo of the Cape buffalo subspecies were used in this study. SNPs (n = 69), with predicted functional consequences in genes related to the immune system, were genotyped in this buffalo population by competitive allele-specific SNP genotyping. Case-control association testing and statistical analyses identified three SNPs associated with BTB status in buffalo. These SNPs, SNP41, SNP137 and SNP144, are located in the SLC7A13, DMBT1 and IL1α genes, respectively. SNP137 remained significantly associated after permutation testing. The three genetic polymorphisms identified are located in promising candidate genes for further exploration into genetic susceptibility to BTB in buffalo and other bovids, such as the domestic cow. These polymorphisms/genes may also hold potential for marker-assisted breeding programmes, with the aim of breeding more BTB-resistant animals and herds within both the national parks and the private sector.

Su1754 The Crohn's Disease Associated DMBT1 Gene Variant Rs2981804 Influences IL-22-Induced DMBT1 Gene Expression by Modifying the DNA Binding of the Transcription Factors CREB1 and ATF2

Su1754 The Crohn's Disease Associated DMBT1 Gene Variant Rs2981804 Influences IL-22-Induced DMBT1 Gene Expression by Modifying the DNA Binding of the Transcription Factors CREB1 and ATF2

Role of mRNA Expression in the Nasal Polyp Pathogenesis

Objective: Nasal polyposis (NP) not only has a significant impact on the life quality of patients but also affects 2.11% of the population is a chronic inflammatory disease of the upper airway. The aim of this study is to evaluate and understand nasal polyp pathogenesis. Method: Healthy mucosa and polyp samples were taken from 27 patients with nasal polyposis who underwent FESS. Total RNA was extracted from samples and converted to cDNA. Expressions of five given genes namely CC10, DMBT1, LTF, STAT, PIP were detected using QRT-PCR technique. GAPDH gene were used for normalization. Results: While there was no significant change in CC10 expression levels, we observed significant increase in the expressions of DMBT1, LTF, STAT and PIP compared to polyp tissue with healty mucosa. Conclusion: We observed significant changes in the expressions of DMBT1, LTF, STAT and PIP genes which are kniwn with anti-inflammatory, antimicrobial, immunomodulatory, and antineoplastic properties.

Identification of Novel DMBT1 Gene Variants as Susceptibility Variants for Crohn's Disease and Ulcerative Colitis

Identification of Novel DMBT1 Gene Variants as Susceptibility Variants for Crohn's Disease and Ulcerative Colitis

Deleted in Malignant Brain Tumors-1 Protein (DMBT1): A Pattern Recognition Receptor with Multiple Binding Sites

Deleted in Malignant Brain Tumors-1 protein (DMBT1), salivary agglutinin (DMBT1SAG), and lung glycoprotein-340 (DMBT1GP340) are three names for glycoproteins encoded by the same DMBT1 gene. All these proteins belong to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins: a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. In addition to SRCR domains, all DMBT1s contain two CUB domains and one zona pellucida domain. The SRCR domains play a role in the function of DMBT1s, which is the binding of a broad range of pathogens including cariogenic streptococci, Helicobacter pylori and HIV. Mucosal defense proteins like IgA, surfactant proteins and lactoferrin also bind to DMBT1s through their SRCR domains. The binding motif on the SRCR domains comprises an 11-mer peptide in which a few amino acids are essential for binding (GRVEVLYRGSW). Adjacent to each individual SRCR domain are glycosylation domains, where the attached carbohydrate chains play a role in the binding of influenza A virus and Helicobacter pylori. The composition of the carbohydrate chains is not only donor specific, but also varies between different organs. These data demonstrate a role for DMBT1s as pattern recognition molecules containing various peptide and carbohydrate binding motifs.

A microarray study of gene expression profiles in nasal polyps

Objective Nasal polyposis (NP) is a multifactorial disease manifesting in chronic inflammation of upper respiratory tract of unknown etiology. We studied mRNA gene expression profiles in NP compared with normal mucosa as well as pointed at genes characteristic of different expression in examined tissues. Material and methods Fifty-three patients with NP (36 eosinophilic and 17 neutrophilic NP) were included into the study. Transcriptional activity of genes was analyzed using oligonucleotide microarray in 17 NP and 8 cases of normal nasal mucosa. A study of mRNA expression of selected genes was performed using QRT-PCR. Results We identified 556 genes, which were differentially expressed between the studied and the control group. Among them 217 showed significantly higher expression, whereas 339 lower expression in NP than in controls. The microarray and QRT-PCR results were compatible for 7 of 8 evaluated genes. In NP strongly significant higher transcriptional activity of MMP10, NOS2A, ALOX15 and IL-8 genes was observed. In the control group, significantly higher expression of DMBT1, ALOX12 and LTF genes was detected. Conclusion The analysis of gene expression in inflammatory changed nasal polyp tissues may become a supplementary method in diagnostics and treatment. Molecular alterations may indicate changes during the clinical course of the disease.

The construction of gallbladder carcinoma cell line GBC-SD with stable expression of DMBT1 and its growth properties HE Too

Objective To establish the cell line CBC-SD of gallbladder carcinoma with stable expression of a new candidate tumor suppressor gene DMBT1 and analyze its proliferation features. Methods GBC-SD was transfected with the plasmid pTRexDest30_DMBT18kb.2 by Lipofectamine 2000 and subsequently screened with G418 for 5-6 weeks. The expression of DMBT1 niRNA and protein was detected by reverse transcription-PCR, Western blot and immunocytochemistry;cell proliferation was evaluated by MTT method,and cell apoptosis in serum-free medium was assessed with DAPI staining. Results After selection with G418 for 5-6 weeks, macroscopic resistant cell cloning was formed in the experimental group and the control group, whereas all the cells died in the untreated group. RT-PCR and Western blot revealed that the relative expression levels of DMBT1 protein and mRNA in the experimental group were 0. 82±0. 11 and 0. 87±0. 12 respectively,P<0. 01 versus the control group (0.24±0.03 and 0. 29±0. 03 respectively) ,equivalent to the findings of immunocytochemistry. The growth curves indicated that the experimental group showed a slackened pace of proliferation versus the control group, the inhibition ratio of proliferation of cells cultured for 72 h in serum-free medium was (43.3±5.0)%. DAPI staining showed that apoptosis rate of cells culture in serum-free medium in the experimental group was (22.0±2.5)% versus (7.0±1. 1 )% in the control group. Conclusion The gallbladder carcinoma cell line that stably expressed DMBT1 was successfully established. DMBT1 over-expression in vitro suppresses proliferation of the gallbladder carcinoma cells and induces their apoptosis in serum-free medium. Key words: Gallbladder carcinoma; Proliferation; Transfection

Molecular genetics of astrocytomas

Astrocytomas are the most frequent group of intracranial tumors. Among them, glioblastoma is the most aggressive one. In this review we will describe the most common genetic abnormalities found out in astrocytomas. We will refer to the epidermal growth factor receptor (EGFR), p53, p16, PTEN and DMBT1 genes. We will also present certain genetic aspects that influence the progression to glioblastoma.

Expression of DMBTI in liver cirrhosis and its relation to oval cell proliferation

Objective To investigate the expression of DMBT1 in liver cirrhosis and its relation to oval cell proliferation.Methods Immunostaining was carried out for CK19, Hep and DMBT1 in 22 liver cirrhotic samples.The homozygous deletion of DMBT1 in proliferated bile ductules (PBD) was investigated by laser capture microdissection (LCM).Meanwhile, the samples from 5 cases were ex-amined with transmission electron microscopy.Ten normal liver tissues were used as controls.Results Microscopically, oval cells could be found in all cirrhotic cases which could coexpress CK19 and Hep and its number was found to increase significantly with the progression of inflammation.Electron mi-croscope identified the presence of oval cells in PBD.DMBT1 could express in these cells too and its positive rate in PBD was 45.5 %.The homozygous deletion of DMBT1 was found in 45.5% PBD.In normal liver tissues, PBD and oval cells were not found.DMBT1 expression was only detectable in few large bile ducts.Conclusion There are bipotent oval cells with high expression of DMBT1 in liver cirrhosis hiding in PBD and DMBT1 can be specifically deleted in PBD, suggesting that DMBT1 may be related to the proliferation of oval cells and may participate in the development of liver cirrhosis. Key words: Liver cirrhosis; Oval cell; DMBT1; Laser capture microdisseetion; Allelic deletion

Secreted Cyclophilin A, a Peptidylprolyl cis-trans Isomerase, Mediates Matrix Assembly of Hensin, a Protein Implicated in Epithelial Differentiation

Hensin is a rabbit ortholog of DMBT1, a multifunctional, multidomain protein implicated in the regulation of epithelial differentiation, innate immunity, and tumorigenesis. Hensin in the extracellular matrix (ECM) induced morphological changes characteristic of terminal differentiation in a clonal cell line (clone C) of rabbit kidney intercalated cells. Although hensin is secreted in monomeric and various oligomeric forms, only the polymerized ECM form is able to induce these phenotypic changes. Here we report that hensin secretion and matrix assembly were inhibited by the peptidylprolyl cis-trans isomerase (PPIase) inhibitors cyclosporin A (CsA) and a derivative of cyclosporin A with modifications in the d-Ser side chain (Cs9) but not by the calcineurin pathway inhibitor FK506. PPIase inhibition led to failure of hensin polymerization in the medium and ECM, plus the loss of apical cytoskeleton, apical microvilli, and the columnar epithelial shape of clone C cells. Cyclophilin A was produced and secreted into the media to a much greater extent than cyclophilins B and C. Our results also identified the direct CsA-sensitive interaction of cyclophilin A with hensin, suggesting that cyclophilin A is the PPIase that mediates the polymerization and matrix assembly of hensin. These results are significant because this is the first time a direct role of peptidylprolyl cis-trans isomerase activity has been implicated in the process of epithelial differentiation.

Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

The Dmbt1 gene encodes alternatively spliced glycoproteins that are either membrane-associated or secreted epithelial products. Functions proposed for Dmbt1 include it being a tumor suppressor, having roles in innate immune defense and inflammation, and being a Golgi-sorting receptor in the exocrine pancreas. The heavily sulfated membrane glycoprotein mucin-like glycoprotein (Muclin) is a Dmbt1 product that is strongly expressed in organs of the gastrointestinal (GI) system. To explore Muclin's functions in the GI system, the Dmbt1 gene was targeted to produce Muclin-deficient mice. Muclin-deficient mice have normal body weight gain and are fertile. The Muclin-deficient mice did not develop GI tumors, even when crossed with mice lacking the known tumor suppressor p53. When colitis was induced by dextran sulfate sodium, there was no significant difference in disease severity in Muclin-deficient mice. Also, when acute pancreatitis was induced with supraphysiological caerulein, there was no difference in disease severity in the Muclin-deficient mice. Exocrine pancreatic function was impaired, as measured by attenuated neurohormonal-stimulated amylase release from Muclin-deficient acinar cells. Also, by [(35)S]Met/Cys pulse-chase analysis, traffic of newly synthesized protein to the stimulus-releasable pool was significantly retarded in Muclin-deficient cells compared with wild type. Thus Muclin deficiency impairs trafficking of regulated proteins to a stimulus-releasable pool in the exocrine pancreas.

Salivary agglutinin/glycoprotein-340/DMBT1: a single molecule with variable composition and with different functions in infection, inflammation and cancer

Salivary agglutinin (SAG), lung glycoprotein-340 (gp-340) and Deleted in Malignant Brain Tumours 1 (DMBT1) are three names for identical proteins encoded by the dmbt1 gene. DMBT1/SAG/gp-340 belongs to the scavenger receptor cysteine-rich (SRCR) superfamily of proteins, a superfamily of secreted or membrane-bound proteins with SRCR domains that are highly conserved down to sponges, the most ancient metazoa. On the one hand, DMBT1 may represent an innate defence factor acting as a pattern recognition molecule. It interacts with a broad range of pathogens, including cariogenic streptococci and Helicobacter pylori, influenza viruses and HIV, but also with mucosal defence proteins, such as IgA, surfactant proteins and MUC5B. Stimulation of alveolar macrophage migration, suppression of neutrophil oxidative burst and activation of the complement cascade point further to an important role in the regulation of inflammatory responses. On the other hand, DMBT1 has been demonstrated to play a role in epithelial and stem cell differentiation. Inactivation of the gene coding for this protein may lead to disturbed differentiation, possibly resulting in tumour formation. These data strongly point to a role for DMBT1 as a molecule linking innate immune processes with regenerative processes.

Genetic profiling of a distant second glioblastoma multiforme after radiotherapy: recurrence or second primary tumor?

In nearly all patients with glioblastoma multiforme (GBM) a local recurrence develops within a short period of time. In this paper the authors describe two patients in whom a second GBM developed after a relatively long time interval at a site remote from the primary tumor. The genetic profiles of the tumors were compared to discriminate between distant recurrence and a second primary tumor. Both patients harboring a supratentorial GBM were treated with surgery and local high-dose radiotherapy. Local control of the disease at the primary tumor site was achieved. Within 2 years, a second GBM developed in both patients, not only outside the previously irradiated target areas but infratentorially in one patient and in the opposite hemisphere in the other. The tumors were examined for the presence of several genetic alterations that are frequently found in GBMs--a loss of heterozygosity at chromosome regions 1p36, 10pl5, 19q13, and 22q13, and at the CDKN2A, PTEN, DMBT1, and TP53 gene regions; a TP53 mutation; and EGFR amplification. In the first patient, genetic profiling revealed that the primary tumor had an allelic imbalance for markers in several chromosome regions for which the second tumor displayed a complete loss. In the second patient, genetic profiling demonstrated the presence of genetic changes in the second tumor that were identical with and additional to those found in the primary tumor. Based on the similarities between the genetic profiles of the primary and the second tumors in these patients, the authors decided that in each case the second distant GBM was a distant recurrence rather than a second independent primary tumor.

Single nucleotide polymorphisms in the DMBT1 promoter and the progression of breast cancer

Department of Public Health and Clinical Medicine/Nutritional Research, Umea University, Sweden˚Dear Sir,The gene, deleted in malignant brain tumors 1 (DMBT1,OMIM 601969), locating in chromosome 10q25-26, has beensuggested to be a putative candidate tumor suppressor gene inepithelial cancers. Loss or decreased DMBT1 gene expressionhas been originally reported in brain tumors