DMBT1 expression is down-regulated in breast cancer.
BACKGROUND
We studied the expression of DMBT1 (deleted in malignant brain tumor 1), a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle.


METHODS
Sections from 17 benign lesions and 55 carcinomas were immunostained with anti DMBT1 antibody (DMBTh12) and sections from 36 samples, were double-stained also with anti MCM5, one of the 6 pre-replicative complex proteins with cell proliferation-licensing functions. DMBT1 gene expression at mRNA level was assessed by RT-PCR in frozen tissues samples from 39 patients.


RESULTS
Normal glands and hyperplastic epithelium in benign lesions displayed a luminal polarized DMBTh12 immunoreactivity. Normal and hyperplastic epithelium adjacent to carcinomas showed a loss of polarization, with immunostaining present in basal and perinuclear cytoplasmic compartments. DMBT1 protein expression was down-regulated in the cancerous lesions compared to the normal and/or hyperplastic epithelium adjacent to carcinomas (3/55 positive carcinomas versus 33/42 positive normal/hyperplastic epithelia; p = 0.0001). In 72% of cases RT-PCR confirmed immunohistochemical results. Most of normal and hyperplastic mammary cells positive with DMBTh12 were also MCM5-positive.


CONCLUSIONS
The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. Moreover, the concomitant expression of DMTB1 and MCM5 suggests its possible association with the cell-cycle regulation.
University of Milano, Department of Medicine, Surgery and Dentistry, S. Paolo Hospital and IRCCS Ospedale Maggiore, Milan, Italy. paola.braidotti@unimi.it
P
P
Braidotti
P G
PG
Nuciforo
J
J
Mollenhauer
A
A
Poustka
C
C
Pellegrini
A
A
Moro
G
G
Bulfamante
G
G
Coggi
S
S
Bosari
G G
GG
Pietra
D000373:Agglutinins / Q000378:metabolism*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002135:Calcium-Binding Proteins; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004848:Epithelium / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins
D000373:Agglutinins; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; C489423:MCM5 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins