期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 47, 期 2, 页码 650-656出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2015.3030
关键词
estrogen biphasic effect; claudin-4; endometrium
类别
资金
- National Science Foundation Major Research Instrumentation (NSF-MRI) Grant [0922258]
- NSF-MRI [1229702]
- Joe and Jessie Crump Fund at JP Morgan Bank
- ACS Andrew W. Mellon Integrated Scholarly Grant
- Howard Hughes Medical Institute through the Undergraduate Science Education Program [52007558]
- Sam Taylor Fellowship
- Southwestern University Faculty-Student Collaborative Projects
- Div Of Biological Infrastructure
- Direct For Biological Sciences [1229702] Funding Source: National Science Foundation
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0922258] Funding Source: National Science Foundation
Endometrial cancer is the most common female reproductive cancer in the United States and is associated with deregulated tight junction protein expression. Given the highly estrogen-responsive nature of this tissue, we investigated the effects of estrogen and its agonist, 4-OH TAM, on the expression and subcellular localization of the tight junction protein claudin-4 (CLDN-4), in HEC-1A endometrial cancer cells. In untreated HEC-1A cells, we observed dramatic overexpression of claudin-4 protein. In addition, differential detergent extraction analysis indicated that claudin-4 was localized primarily in the membrane but also found in the cytosolic, nuclear and cytoskeletal fractions. Upon exposure of HEC-1A to estradiol (E-2), we observed a biphasic effect both on the overall expression of claudin-4 protein and on its cytosolic and cytoskeletal presence as demonstrated by immunoblot analysis. Immunofluorescence analysis also revealed a biphasic effect of E-2, on claudin-4 expression. In contrast, we observed no changes in expression levels nor in the subcellular distribution patterns of claudin-4 in HEC-1A cells treated with different concentrations of 4-OH TAM. The intracellular presence of CLDN-4 coupled with the biphasic effects of E-2 on CLDN-4 expression in the cytoskeleton suggest that this protein may be involved in cell signaling to and from TJs.
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