Expression of tight and adherens junction proteins in cervical neoplasia

Abstract

ABSTRACTAdherens junctions (AJ) and tight junctions (TJ) play a key role in maintaining the apical-basolateral polarity and cohesive structure of epithelial cells. These epithelial junctions are maintained by the interaction of several key proteins including E-cadherin, claudins, occludin and zona-occludens. The zinc finger protein, Snail, has previously been identified as a possible regulator of several of these AJ and TJ proteins. Expression levels of ZO-1, occludin, claudins, E-cadherin, human Scribble protein and Snail were determined in HeLa and CaSki cervical carcinoma cell lines by imuunohistochemistry (IHC) and Western blotting. In tandem, tissue microarrays were utilised in the IHC-based detection of E-cadherin in 26 cases of non-cancerous cervical tissue, 15 cases of cervical intraepithelial neoplasia 1 (CIN1), 11 cases of CIN2, 12 cases of CIN3, 50 cases of squamous cell carcinoma and two cases of adenocarcinoma. This study found aberrant E-cadherin expression in CIN lesions and cases of squamous cell carcinoma compared to normal epithelium. HeLa cells were E-cadherin-negative while CaSki cells were positive, with HeLa cells showing a high level of Snail expression. Occludin and ZO-1 expression was detected in both cell lines. No expression was observed for claudin 1 or claudin 5 tight junction proteins in HeLa cells or CaSki cells. Loss of expression of claudin 1, claudin 5 and E-cadherin, with concomitant increase in Snail may be associated with loss of epithelial cell polarity and alterations in intercellular adhesion.