Sequential changes of the DMBT1 expression and location in normal lung tissue and lung carcinomas.
Deleted in Malignant Brain Tumors 1 (DMBT1) at chromosome region 10q25.3-q26.1 has been proposed as a candidate tumor-suppressor gene for brain, digestive tract, and lung cancer. Recent studies on its expression in lung cancer have led to divergent results and have raised a controversial discussion. Moreover, DMBT1 has been implicated with epithelial protection in the respiratory tract. We thus wondered how a loss of its expression could be related to carcinogenesis in the lung. To address these issues, we investigated the DMBT1 expression and location in the normal lung and lung cancer. By reverse-transcription PCR, a down-regulation of the DMBT1 expression in lung cancer cell lines is commonly detected. Immunohistochemical studies in situ demonstrate that there are also low steady-state levels of DMBT1 in the normal respiratory epithelium. However, an up-regulation takes place in the tumor-flanking epithelium and upon respiratory inflammation. Lung carcinomas show increased DMBT1 expression compared to that of undiseased lung tissue, but decreased DMBT1 levels compared to that of tumor-flanking and inflammatory tissue. A switch from a lumenal secretion to a secretion to the extracellular matrix takes place during lung carcinogenesis. Our data may resolve the controversial discussion on its expression in lung carcinomas. We hypothesize that the changes of the DMBT1 expression and location do reflect a time course that may point to possible mechanisms for its role in epithelial cancer.
Mollenhauer
Jan
J
Department of Molecular Genome Analysis, Deutsches Krebsforschungszentrum, Heidelberg, Germany. j.mollenhauer@dkfz.de
Helmke
Burkhard
B
Müller
Hanna
H
Kollender
Gaby
G
Lyer
Stefan
S
Diedrichs
Laura
L
Holmskov
Uffe
U
Ligtenberg
Toon
T
Herbertz
Stephan
S
Krebs
Inge
I
Wiemann
Stefan
S
Madsen
Jens
J
Bikker
Floris
F
Schmitt
Liane
L
Otto
Herwart F
HF
Poustka
Annemarie
A
D000328:Adult; D000373:Agglutinins; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000378:metabolism / 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