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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000397-02
Application #
7963965
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2009
Total Cost
$213,405
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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 :
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