We have used a variety of approaches to characterize the patterns of claudin-7 expression in ovarian cancer. In addition, in order to identify the roles of claudin-7 in tumorigenesis, we have used RNAi technology to knockdown CLDN7 in two ovarian cancer cell lines (OVCA420 and OVCAR-2). Using this model, the effects of CLDN7 knockdown on proliferation, motility, and tight junction function have been studies. Illumina oligonucleotide arrays were then used to identify genes affected by CLDN7 down-regulation. We have identified several genes differentially expressed following CLDN7 knockdown. Interestingly, 200 genes were upregulated in both cell lines and 97 were downregulated in both cell lines. We are currently validating these genes and identifying pathways that may be important downstream of claudin-7. Once pathways are identified, we will use transfections and RNAi approaches to clarify the roles of these pathways in the transduction of claudin-7 signals. Interestingly, we have found that similar to claudin-3 and -4, claudin-7 can affect migration and invasion of ovarian cancer cells.
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