DMBT1 expression is down-regulated in breast cancer.

P Braidotti,J Mollenhauer,G Coggi,Pg Nuciforo,A Moro,A Poustka,C Pellegrini,G Bulfamante,S Bosari,Gg Pietra

doi:10.1186/1471-2407-4-46

Abstract

BackgroundWe 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.MethodsSections 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.ResultsNormal 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.ConclusionsThe 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.

Highlights

We studied the expression of DMBT1, a putative tumor suppressor gene, in normal, proliferative, and malignant breast epithelium and its possible relation to cell cycle
Mannan binding protein (MBP), has been shown to have an anti tumour effect against gliomas and colorectal carcinomas in vitro and in vivo [18,19]. While this anti tumor property remains to be demonstrated for Sp-A and Sp-D, we have previously reported the presence of surfactant protein A (Sp-A) in the ductal epithelium of the normal breast and its variable expression in mammary carcinomas
We examined in morphologically normal epithelium a possible association of DMBT1 expression with that of an early proliferative marker such as MCM5 (Minichromosome Maintenance protein 5)

Summary

Methods

Sections from 17 benign lesions and 55 carcinomas were immunostained with anti DMBT1 antibody (DMBTh12) and sections from 36 samples, were double-stained 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. Tissue and cell-lines From the files of the Surgical Pathology at S.Paolo University Hospital, we retrieved paraffin blocks of 72 consecutive breast lesions surgically resected. This material included 16 cases of fibrocystic disease (FD), 1 case of gynecomastia (GM), 10 samples of ductal carcinoma in situ (DCIS) and 45 cases of infiltrating carcinoma (IC) (36 ductal, 2 lobular, 2 mixed lobular and ductal, 2 mucinous, 1 apocrine, 1 cribriform, 1 papillary). We analysed by RT-PCR two breast cancer cell lines (Hs578T and T-47D) obtained from the American Type Culture Collection and maintained as recommended

Results

Discussion

Conclusion