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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000397-01
Application #
7732233
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2008
Total Cost
$223,550
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Lal-Nag, Madhu; Morin, Patrice J (2009) The claudins. Genome Biol 10:235
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
Morin, Patrice J (2007) Claudin proteins in ovarian cancer. Dis Markers 23:453-7