The claudin gene family: expression in normal and neoplastic tissues

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Abstract
Background: The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent thatCLDNgene expression is frequently altered in several human cancers. However, the exact patterns ofCLDNexpression in various cancers is unknown, as only a limited number ofCLDNgenes have been investigated in a few tumors.Methods: We identified all the humanCLDNgenes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21CLDNin 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13CLDNgenes in 24 normal and 24 neoplastic tissues.Results: We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. Fromin silicoanalysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, whileCLDN3,CLDN4, andCLDN7are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly,CLDN5is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy.CLDN18might represent a biomarker for gastric cancer.Conclusion: Our study confirms previously knownCLDNgene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that expressCLDN3andCLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4.