| Breast carcinoma is a type of malignant tumors derived from the epithelium of breast. Tight junctions (TJs) are the major apical component of the epithelial, endothelial and sheath cell junctional complex. The barrier function of TJs is necessary for maintaining homeostasis and involved in the establishment of cell polarity. It plays an important role in regulating cell proliferation and differentiation and in transmissing signals between cells. The abnormalities of TJs in structure impair its function resulting in the instability of microenvironment, the loss of cell polarity and decontrol of cell proliferation and growth on which growth of cancer cells, infiltrate and metastasis based. TJs exit as multimolecular complexes composed of several types of transmembrane, cytoplasmic and signal proteins. Occludin, claudins, Junction adhesion molecule (JAM) belong to transmembrane proteins; Zos and MUPP-1 are cytoplasmic proteins; protein kinase C (PKC) belongs to signal protein. Claudins are the most important ingredients of TJs. They play important roles in maintaining the integrity of the structure and function as epidermal permeability barrier (EPB). The loss of cell polarity derived from disruption of the EPB constitutes one of the key steps for the tumor genesis in epithelial tissues. Hence, the structural abnormalities of TJs result from the reduced expression of claudins play an important role in tumor genesis and metastasis. Occludin is first found transmembrane proteins. It plays an important role in maintaining cell adhesion, suppressing cell migration and infiltration and signal transmission. It is believed that occludin might function as a candidate gene for tumor suppression.The structure and function of TJs are modulated by many factors. PKC is a phospholipids dependent protein kinase which functions as a major signals in cell proliferation, differentiation and apoptosis and plays key roles in maintaining the function of TJs. Little is known on the expression of claudin-6, occludin, PKCθinvolved in breast carcinoma. Specific aim of this study is to show the differential expression profile of claudin-6, occludin, and PKCθgenes in various differentiation, clinical stages, and metastasis and to analyze the roles of these proteins in the genesis and progress of breast carcinomas.The expression of claudin-6, occludin, and PKCθin 39 breast carcinomas and 11 laterocarconoma normal breast tissue by using immunohistochemistry method with the goat polyclonal anybody against human clauidn-6, rabbitpolyclonal antibody against human occludin, mouse monoclonal antibody against human PKCθ. Results are as following:1. The positive rate of claudin-6 was 90.91% (10/11) in laterocarcinoma normal breast tissue and 66.67% (26/39) in breast carcinoma tissue. The former was higher than the latter, but the difference is statistically not significant (P>0.05). The levels of claudin-6 was not dependent on the degree of tissue differentiation, clinical stages, metastasis in lymph node and the ages of patients (P>0.05).2. The positive rate of occludin was 100% (11/11) in laterocarcinoma normal breast tissue and 89.74% (35/39) in breast carcinoma, significantly higher in the former than in the latter (P<0.05). The positive rates of occludin decreased following the histopathological phases (P<0.05), but keep no changes with the degree of tissue differentiation, metastasis in lymph node and the ages of patients (P>0.05).3.The positive rate of PKCθwas 36.36%(4/11) in laterocarcinoma normal breast tissue and 53.85% (21/39) in breast carcinoma tissue, the former was significant lower than the latter(P>0.05). There is a tendency of increase in the positive rates in PKCθfollowing higher differentiation, with the increases of pathological phase and the metastasis in lymph nodes of breast carcinoma, but the difference did not reach the statistically significant level (P>0.05). The positive rates of PKCθincreased following the ages of patients(P<0.05).4. Statistical analysis in the expressions of claudin-6, occludin and PKCθin breast carcinomas did not show any significant relations between any two of them (P>0.05).Our results suggest that the lower expression of claudin-6 and occludin and the higher expression of PKCθprobably play important roles by effecting the structure and function of TJs in the development of breast carcinoma. The reduced expression of occludin could be useful as a reference parameter to estimate the tumor growth, dissemination, and progress. Further study is required for the detail functions of claudin-6, occludin and PKCθin the genesis and development and metastasis of breast carcinoma. |
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