Zusammenfassung
Human claudin-1 is an integral protein component of tight junctions, a structure controlling cell-to-cell adhesion and, consequently, regulating paracellular and transcellular transport of solutes across human epithelia and endothelia. Recently, a claudin-1 (CLDN1) cDNA has been isolated from human mammary epithelial cells (HMECs). CLDN1 expression in HMECs, in contrast to low or undetectable ...
Zusammenfassung
Human claudin-1 is an integral protein component of tight junctions, a structure controlling cell-to-cell adhesion and, consequently, regulating paracellular and transcellular transport of solutes across human epithelia and endothelia. Recently, a claudin-1 (CLDN1) cDNA has been isolated from human mammary epithelial cells (HMECs). CLDN1 expression in HMECs, in contrast to low or undetectable levels of expression in a number of breast tumors and breast cancer cell lines, points to CLDN1 as a possible tumor-suppressor gene. In order to evaluate the CLDN-1 gene in sporadic and hereditary breast cancer, we have characterized its genomic organization and have screened the four coding exons for somatic mutations in 96 sporadic breast carcinomas and for germline mutations in 93 breast cancer patients with a strong family history of breast cancer. In addition, we have compared the 5'-upstream sequences of the human and murine CLDN1 genes to identify putative promoter sequences and have examined both the promoter and coding regions of the human gene in the breast cancer cell lines showing decreased CLDN1 expression. In the sporadic tumors and hereditary breast cancer patients, we have found no evidence to support the involvement of aberrant CLDN1 in breast tumorigenesis. Likewise, in the breast cancer cell lines, no genetic alterations in the promoter or coding sequences have been identified that would explain the loss of CLDN1 expression. Other regulatory or epigenetic factors may be involved in the down-regulation of this gene during breast cancer development.
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