An integrative model on the role of DMBT1 in epithelial cancer.
The gene, deleted in malignant brain tumors 1 (DMBT1), has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumor suppressor gene. We have proposed that its presumptive dual function in protection and differentiation is of importance to understand its role in cancer. To gain insights into its role in tumorigenesis, we conducted a comprehensive study on DMBT1 mutations, expression and location. Twenty-one out of 44 tumors showed variable numbers of tandem repeats (VNTRs) due to genetic polymorphism of DMBT1, whereas 11 out of 44 tumors displayed presumable mutations. However, none of the alterations would be predicted to lead to a complete inactivation of the gene. DMBT1 is mucin-like and shows tissue-specific expression and secretion, pointing to a function in the protection of monolayered epithelia and to an additional function in the differentiation of multilayered epithelia. The expression patterns in carcinomas arising from the respective structures support this view. Accepting this functional dualism gives rise to an initial model on the role of DMBT1 in epithelial cancer.
Mollenhauer
Jan
J
j.mollenhauer@dkfz.de
Helmke
Burkhard
B
Müller
Hanna
H
Kollender
Gaby
G
Krebs
Inge
I
Wiemann
Stefan
S
Holmskov
Uffe
U
Madsen
Jens
J
Otto
Herwart F
HF
Poustka
Annemarie
A
D000373:Agglutinins; D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019656:Loss of Heterozygosity; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D009928:Organ Specificity; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins