Silencing of IQGAP1 by shRNA inhibits the invasion of ovarian carcinoma HO-8910PM cells in vitro.
BACKGROUND
IQGAP1 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.


METHODS
We 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.


RESULTS
IQGAP1 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.


CONCLUSIONS
Our 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.
Dong
Pei-Xin
PX
Hospital and Institute of Obstetrics and Gynecology, Fudan University Shanghai Medical, College, Shanghai, PR China. dpx1cn@yahoo.com.cn
Jia
Nan
N
Xu
Zhu-Jie
ZJ
Liu
Ying-Tao
YT
Li
Da-Jin
DJ
Feng
You-Ji
YJ
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D055029:Inverted Repeat Sequences; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D034622:RNA Interference; D022661:RNA, Untranslated / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
C101203:IQ motif containing GTPase activating protein 1; D022661:RNA, Untranslated; D020703:ras GTPase-Activating Proteins