Claudin 7 expression and localization in the normal murine mammary gland and murine mammary tumors

Breast Cancer Research

Margaret C Neville¹  Daniel Medina²  Steven K Nordeen¹  Tanya Russell¹  Brigitte Blackman¹ 

[1] University of Colorado Health Sciences Center, Denver, Colorado, USA;Baylor College of Medicine, Houston, Texas, USA

关键词: tight junction;    mammary tumors;    mammary development;    EPH4 cells;    claudin;   

Others  :  1114986
DOI  :  10.1186/bcr988

 received in 2004-08-03, accepted in 2004-12-10,  发布年份 2005

【 摘 要 】

Introduction

Claudins, membrane-associated tetraspanin proteins, are normally associated with the tight junctions of epithelial cells where they confer a variety of permeability properties to the transepithelial barrier. One member of this family, claudin 7, has been shown to be expressed in the human mammary epithelium and some breast tumors. To set the stage for functional experiments on this molecule, we examined the developmental expression and localization of claudin 7 in the murine mammary epithelium and in a selection of murine mammary tumors.

Method

We used real-time polymerase chain reaction, in situ mRNA localization, and immunohistochemistry (IHC) to examine the expression and localization of claudin 7. Frozen sections were examined by digital confocal microscopy for colocalization with the tight-junction protein ZO1.

Results

Claudin 7 was expressed constitutively in the mammary epithelium at all developmental stages, and the ratio of its mRNA to that of keratin 19 was nearly constant through development. By IHC, claudin 7 was located in the basolateral part of the cell where it seemed to be localized to discrete vesicles. Scant colocalization with the tight-junction scaffolding protein ZO1 was observed. Similar results were obtained from IHC of the airway epithelium and some renal tubules; however, claudin 7 did partly colocalize with ZO1 in EPH4 cells, a normal murine mammary cell line, and in the epididymis. The molecule was localized in the cytoplasm of MMTV-neu and the transplantable murine tumor cell lines TM4, TM10, and TM40A, in which its ratio to cytokeratin was higher than in the normal mammary epithelium.

Conclusion

Claudin 7 is expressed constitutively in the mammary epithelium at approximately equal levels throughout development as well as in the murine tumors examined. Although it is capable of localizing to tight junctions, in the epithelia of mammary gland, airway, and kidney it is mostly or entirely confined to punctate cytoplasmic structures, often near the basolateral surfaces of the cells and possibly associated with basolateral membranes. These observations suggest that claudin 7 might be involved in vesicle trafficking to the basolateral membrane, possibly stabilizing cytoplasmic vesicles or participating in cell–matrix interactions.

【 授权许可】

   
2005 Blackman et al.; licensee BioMed Central Ltd.

【 图 表 】

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