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.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Dahiya, Neetu; Becker, Kevin G; Wood 3rd, William H et al. (2011) Claudin-7 is frequently overexpressed in ovarian cancer and promotes invasion. PLoS One 6:e22119
Ramalingam, Arivudainambi; Wang, Xuexuan; Gabello, Melissa et al. (2010) Dietary Methionine Restriction Improves Colon Tight Junction Barrier Function and Alters Claudin Expression Pattern. Am J Physiol Cell Physiol :
Li, Jianghong; Sherman-Baust, Cheryl A; Tsai-Turton, Miyun et al. (2009) Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer. BMC Cancer 9:244
D'Souza, Theresa; Sherman-Baust, Cheryl A; Poosala, Suresh et al. (2009) Age-related changes of claudin expression in mouse liver, kidney, and pancreas. J Gerontol A Biol Sci Med Sci 64:1146-53
Lal-Nag, Madhu; Morin, Patrice J (2009) The claudins. Genome Biol 10:235