Abstract
BackgroundIQGAP1 is a scaffolding protein and overexpressed in many human tumors, including ovarian cancer. However, the contribution of IQGAP1 to invasive properties of ovarian cancer cells remains unknown. Here, we investigated the effect of IQGAP1-specific short hairpin RNA (shRNA) expressing plasmids on metastatic potential of ovarian cancer HO-8910PM cells.MethodsWe used RT-PCR and Western blot analysis to characterize expression of IQGAP1 in three human ovarian cancer-derived cell lines SK-OV-3, HO-8910 and HO-8910PM. We then determined whether expression of endogenous IQGAP1 correlated with invasive and migratory ability by using an in vitro Matrigel assay and cell migration assay. We further knocked down IQGAP1 using shRNA expressing plasmids controlled by U1 promoter in HO-8910PM cells and examined the proliferation activity, invasive and migration potential of IQGAP1 shRNA transfectants using MTT assay, in vitro Matrigel-coated invasion assay and migration assay.ResultsIQGAP1 expression level seemed to be closely associated with the enhanced invasion and migration in ovarian cancer cell lines. Levels of both IQGAP1 mRNA and protein were significantly reduced in HO-8910PM cells transfected with plasmid-based IQGAP1-specific shRNAs. RNAi-mediated knockdown of IQGAP1 expression in HO-8910PM cells resulted in a significant decrease in cell invasion and migration.ConclusionOur findings support the hypothesis that IQGAP1 promotes tumor progression and identify IQGAP1 as a potential therapeutic strategy for ovarian cancer and some other tumors with over-expression of the IQGAP1 gene.
Highlights
IQGAP1 is a scaffolding protein and overexpressed in many human tumors, including ovarian cancer
We have reported that IQGAP1 was overexpressed in ovarian adenocarcinomas compared with adenomas and borderline tumors and its expression significantly correlated with poor prognosis in patients with ovarian carcinomas [10]
We examined the effects of IQGAP1 silencing on cell invasion and migration, and explored it as a therapeutic target for metastasis of human ovarian carcinoma cells
Summary
IQGAP1 is a scaffolding protein and overexpressed in many human tumors, including ovarian cancer. Journal of Experimental & Clinical Cancer Research 2008, 27:77 http://www.jeccr.com/content/27/1/77 at 15–30% [2] These poor outcomes are due mainly to the progression and metastasis of the disease after the standard surgical treatment. We have reported that IQGAP1 was overexpressed in ovarian adenocarcinomas compared with adenomas and borderline tumors and its expression significantly correlated with poor prognosis in patients with ovarian carcinomas [10]. These lines of evidence have suggested the functional linkage between IQGAP1 and ovarian cancer invasion. The exact mechanisms by which IQGAP1 regulates invasion and metastasis of ovarian carcinomas have not yet been elucidated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
