Zonula occludens-1
(ZO-1)

Tight junction protein 1 (TJP1)

Gene: TJP1 maps to 15q13.
mRNA: size: 7.9 kb.
Protein: a 200-kD protein located on a cytoplasmic membrane surface of vertebrate intercellular tight junctions (TJ). TJ play a crucial role in maintening the selective-barrier function of cell sheets. In TJ, adjacent epithelial cells are fused along a series of matching ridges. The greater number of fused ridges, the tighter the junction. TJ are found in luminal surface of epithelia where it is imperative that luminal substances do not pass between the epithelial cells. Thus the passage of material is controlled, since material can only pass through the cell membrane.

Cell lines:
- ZO-1 was found in BT483, MDA-MB-175, MCF-7, ZR-75-B, T-47D, SK-BR-3, CAMA-1, and MDA-MB-436 breast cancer cell (BCC) lines, but not in BT474, BT549, MDA-MB-134, -231, -361, -435, -453, -468, Hs578T, and MCF-7/Adr (doxorubicin-resistant) BCC lines (Sommers C.L. et al., 1994).

Tumors:
- The expression and subcellular localization of ZO-1 and E-cadherin were investigated in paraffin-embedded breast cancer samples, using immunohistochemistry and confocal microscopy. While normal tissue showed intense staining for ZO-1 at the position of the epithelial tight junctions, this staining was reduced or lost in 69% of breast cancers analyzed (n = 48). ZO-1 staining was positively correlated with tumor differentiation (P = .011) and more specifically with the glandular differentiation of tumors (P = .0019). Reduction in ZO-1 staining was strongly correlated with reduced E-cadherin staining (P = 4.9 x 10^-5). The results suggest that down-regulation of ZO-1 expression and its failure to accumulate at cell junctions may be causally related to cancer progression. To detect loss of heterozygosity, the ZO-1 gene was mapped relative to other markers in 15q13 and polymorphic markers flanking the gene were identified. The marker D15S1019 showed loss of heterozygosity in 23% of informative tumors (n = 13). This suggests that genetic loss may, in some cases, be responsible for the reduction in ZO-1 expression in breast cancer (Hoover K.B. et al., 1998).

Hoover K.B. et al. (1998) Loss of the tight junction MAGUK ZO-1 in breast cancer: relationship to glandular differentiation and loss of heterozygosity. Am. J. Pathol. 153, 1767-1773.
Mohandas T.K. et al. (1995) Localization of the tight junction protein gene TJP1 to human chromosome 15q13, distal to the Prader-Willi/Angelman region, and to mouse chromosome 7. Genomics 30:594-597.
Sommers C.L. et al. (1994) Differentiation state and invasiveness of human breast cancer cell lines. Breast Cancer Res. Treat. 31, 325-335.
Willott E. et al. (1993) The tight junction protein ZO-1 is homologous to the Drosophila discs-large tumor suppressor protein of septate junctions. Proc. Natl. Acad. Sci. USA 90, 7834-7838.

Under construction