Abstract 3127: Expression and sub-cellular localization of claudin-4 in MCF-7 breast and HEC-1A endometrial cancer cell lines

Abstract

Abstract The claudin (CLDN) family consists of 24 tetraspan membrane proteins that are essential for the formation of tight junctions (TJs). Members of the CLDN family display tissue-specific expression and are involved in multiple normal cellular processes. In addition, alterations in CLDN gene expression have been shown to be associated with a variety of cancers. For example, CLDN-3 and CLDN-4 have been found to be upregulated in prostate, ovarian and breast cancer. We have previously shown gross overexpression of CLDN-3 in the breast cancer cell lines MCF-7 and MDA-MB-415. Furthermore, using sequential protein extraction techniques we have consistently observed expression of CLDN-3 in all four subcellular fractions of MCF-7 cells with the bulk of expression in the membrane fraction. CLDN-3 and CLDN-4 genes are located within 50 kb on chromosome 7 and their coordinated regulation has been reported in normal, neoplastic tissues and various cancer cell lines. The present study reports the expression and sub-cellular localization of CLDN-4 in a panel of cancer cell lines using immunoblot analysis. Like CLDN-3, overexpression of claudin-4 was observed in the breast cancer cell lines MCF-7 and MDA-MB-415. In addition, we observed expression of CLDN-3 and CLDN-4 in both endometrial (HEC-1A and RL95-2) and prostate (DU-145) cancer cell lines. Sub-cellular localization analysis of MCF-7 cells demonstrated the expression of CLDN-4 in the membrane, nuclear, cytosolic and to a lesser extent in the cytoskeletal fractions. Currently we are investigating the sub-cellular localization of CLDN-3 and 4 in the endometrial and prostate cancer cell lines described above. Recent studies have shown CLNDs to be involved in signaling to and from TJs, conveying important chemical messages for cell proliferation and differentiation. The presence of CLDN-3 and 4 in the cytosol and nucleus observed in this study may indicate their involvement in cell signaling. Alternatively, their unusual localization may be a characteristic of breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3127. doi:10.1158/1538-7445.AM2011-3127