Cell culture model predicts human disease: Altered expression of junction proteins and matrix metalloproteinases in cervical dysplasia

BMC Clinical Pathology

Eeva Auvinen³  Petri Auvinen¹  Jussi Tarkkanen⁴  Mikko Rönty⁴  Niina Kivi² 

[1] DNA Sequencing and Genomics Laboratory, Institute of Biotechnology, University of Helsinki, Helsinki, Finland;Haartman Institute, Department of Virology, University of Helsinki, POB 21 (Haartmaninkatu 3), FIN-00014, Helsinki, Finland;Department of Virology and Immunology, Helsinki University Hospital Laboratory, Helsinki, Finland;Department of Pathology, Helsinki University Hospital Laboratory, Helsinki, Finland

关键词: MMP;    Microarray;    HPV;    E5;    Cytokeratin;    CIN;    Catenin;    Cadherin;   

Others  :  1085393
DOI  :  10.1186/1472-6890-12-9

 received in 2012-07-30, accepted in 2012-07-30,  发布年份 2012

【 摘 要 】

Background

Cervical cancer is necessarily caused by human papillomaviruses, which encode three oncogenes manifesting their functions by interfering with a number of cellular proteins and pathways: the E5, E6, and E7 proteins. We have earlier found in our microarray studies that the E5 oncogene crucially affects the expression of cellular genes involved in adhesion and motility of epithelial cells.

Methods

In order to biologically validate our previous experimental findings we performed immunohistochemical staining of a representative set of tissue samples from different grades of high-risk human papillomavirus associated cervical disease as well as normal squamous and columnar cervical epithelium. Three-dimensional collagen raft cultures established from E5-expressing and control epithelial cells were also examined. The expression of p16, matrix metalloproteinase (MMP) -7, MMP-16, cytokeratin (CK) 8/18, laminin, E-cadherin and beta-catenin was studied.

Results

In agreement with our previous microarray studies, we found intense staining for E-cadherin and beta-catenin in adherens junctions even in high-grade cervical lesions. Staining for MMP-16 was increased in severe disease as well. No significant change in staining for MMP-7 and cytokeratin 8/18 along with the grade of cervical squamous epithelial disease was observed.

Conclusions

Here we have confirmed, using tissue material from human papillomavirus associated lesions, some of the cellular gene expression modifications that we earlier reported in an experimental system studying specifically the E5 oncogene of papillomaviruses. These findings were partially surprising in the context of cervical carcinogenesis and emphasize that the complexity of carcinogenesis is not yet fully understood. Microarray approaches provide a wide overwiev of gene expression in experimental settings, which may yield biologically valid biomarkers for disease diagnostics, prognosis, and follow-up.

【 授权许可】

   
2012 Kivi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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