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Eur J Cancer. 2004 Dec;40(18):2717-25.

Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer.

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Metastasis and Angiogenesis Research Group, Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, Wales CF14 4XN, UK.


The aim of this study was to investigate the expression of Zonula Occludens (ZO) proteins ZO-1, ZO-2 and ZO-3, and MUPP-1 (multi-PDZ domain protein 1), peripheral/plaque proteins that function in maintaining tight junction integrity and in transducing regulatory signalling events in patients with primary breast cancer. Breast cancer primary tumours (n=114) and background tissues (n=30) were processed for quantitative-polymerase chain reaction (PCR) analysis, Western blotting and immunostaining. Standardised transcript levels of ZO-1 and MUPP-1 were significantly lower in patients with metastatic disease compared with those remaining disease-free (DF) (median follow-up 72.2 months). Immunohistochemistry confirmed these results, with decreased levels in ZO-1 staining. For both ZO-1 and ZO-3, staining was confined to the intercellular regions in normal tissue, whereas in tumour tissues staining was diffuse and cytosolic. Q-PCR revealed a reduction in the levels of ZO-1 and MUPP-1 in patients with disease recurrence. Prognostic indicators of breast cancer were also inversely correlated with ZO-1 expression. We conclude that low levels of tight junction plaque molecules, such as ZO-1 and MUPP-1, in breast cancer are associated with poor patients prognosis.

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