Knockdown of polypyrimidine tract-binding protein suppresses ovarian tumor cell growth and invasiveness in vitro

Abstract

Polypyrimidine tract-binding protein (PTB) is an RNAbinding protein with multiple functions in the regulation of RNA processing and IRES-mediated translation. We report here overexpression of PTB in a majority of epithelial ovarian tumors revealed by immunoblotting and tissue microarray (TMA) staining. By western blotting, we found that PTB was overexpressed in 17 out of 19 ovarian tumor specimens compared to their matchednormal tissues. By TMA staining, we found PTB expression in 38 out of 44 ovarian cancer cases but only in two out of nine normal adjacent tissues. PTB is also overexpressed in SV40 large T-antigen immortalized ovarian epithelial cells compared to normal human ovarian epithelial cells. Using doxycycline-inducible small interfering RNA technology, we found that knockdown of PTB expression in the ovarian tumor cell line A2780 substantially impaired tumor cell proliferation, anchorage-independent growth and in vitro invasiveness. These results suggest that overexpression of PTB is an important component of the multistep process of tumorigenesis, and might be required for the development and maintenance of epithelial ovarian tumors. Moreover, because of its novel role in tumor cell growth and invasiveness, shown here for the first time, PTB may be a novel therapeutic target in the treatment of ovarian cancer.

Structure-function relationships of the polypyrimidine tract binding protein

“…These studies have provided meaningful insights into the function of this versatile and ubiquitous protein. Recent studies have shown a role for PTB in ovarian cancer, suggesting that PTB could be a good potential therapeutic target [101]. These structures could, therefore, facilitate the design of a drug against this cancer.…”

Akt phosphorylation of La regulates specific mRNA translation in glial progenitors

“…In addition to the components of translational machinery, RNA-binding proteins are also aberrantly expressed in tumors, including PTB (He et al, 2007), HuR (Lopez de Silanes et al, 2003), KH domain-containing protein, and hnRNPD among others (Gouble et al, 2002), with a direct correlation between abnormal expression of a particular RNA-binding protein and tumor formation (CRD-BP) in breast tissue (Tessier et al, 2004). Furthermore, many RNA-binding proteins have been reported to be direct targets of Akt, including YB-1 (Evdokimova et al, 2006), the tumor suppressor Pdcd4 (Palamarchuk et al, 2005), BRF1 (Benjamin et al, 2006) and KSRP (Gherzi et al, 2006), thus linking the Akt pathway to mRNA silencing, degradation, apoptosis and the Wnt signaling pathway through the promotion of the stabilization of b-catenin mRNA, respectively.…”

Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer

“…In ovarian cancer, PTBP1 levels correlate with the degree of malignancy (9). Higher amounts of PTBP1 occur in advanced, as compared with benign, ovarian tumors, and PTBP1 increases when ovarian epithelial cells are immortalized (9). Removal of PTBP1 from ovarian tumor cells makes cell less proliferated, anchorage-independent growth, and cell invasion.…”

“…PTBP1 also has multiple functions other than pre-mRNA splicing and affects glioma cell invasion (7). In ovarian cancer, PTBP1 levels correlate with the degree of malignancy (9). Higher amounts of PTBP1 occur in advanced, as compared with benign, ovarian tumors, and PTBP1 increases when ovarian epithelial cells are immortalized (9).…”