Loss of tight junction plaque molecules in breast cancer tissues is associated with a poor prognosis in patients with breast cancer.
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.
Martin
Tracey A
TA
Metastasis and Angiogenesis Research Group, Department of Surgery, University of Wales College of Medicine, Heath Park, Cardiff, Wales CF14 4XN, UK. martina1@cf.ac.uk
Watkins
Gareth
G
Mansel
Robert E
RE
Jiang
Wen G
WG
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism*; D062825:Zonula Occludens Proteins; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein
D002352:Carrier Proteins; C111442:MPDZ protein, human; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569046:TJP2 protein, human; C111873:TJP3 protein, human; D062825:Zonula Occludens Proteins; D062826:Zonula Occludens-1 Protein; D062827:Zonula Occludens-2 Protein; D012313:RNA