title: Polypyrimidine tract-binding protein (PTB) differentially affects malignancy in a cell line-dependent manner.
abstract: RNA processing is altered during malignant transformation, and expression of the polypyrimidine tract-binding protein (PTB) is often increased in cancer cells. Although some data support that PTB promotes cancer, the functional contribution of PTB to the malignant phenotype remains to be clarified. Here we report that although PTB levels are generally increased in cancer cell lines from multiple origins and in endometrial adenocarcinoma tumors, there appears to be no correlation between PTB levels and disease severity or metastatic capacity. The three isoforms of PTB increase heterogeneously among different tumor cells. PTB knockdown in transformed cells by small interfering RNA decreases cellular growth in monolayer culture and to a greater extent in semi-solid media without inducing apoptosis. Down-regulation of PTB expression in a normal cell line reduces proliferation even more significantly. Reduction of PTB inhibits the invasive behavior of two cancer cell lines in Matrigel invasion assays but enhances the invasive behavior of another. At the molecular level, PTB in various cell lines differentially affects the alternative splicing pattern of the same substrates, such as caspase 2. Furthermore, overexpression of PTB does not enhance proliferation, anchorage-independent growth, or invasion in immortalized or normal cells. These data demonstrate that PTB is not oncogenic and can either promote or antagonize a malignant trait dependent upon the specific intra-cellular environment.
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine of Northwestern University, Chicago, IL 60611, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: John T
authors.initials: JT
authors.lastname: Norton
authors.forename: Supurna
authors.initials: S
authors.lastname: Ghosh
authors.forename: Julie
authors.initials: J
authors.lastname: Kim
authors.forename: Kazuo
authors.initials: K
authors.lastname: Fushimi
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Wu
authors.forename: M Sharon
authors.initials: MS
authors.lastname: Stack
authors.forename: Sui
authors.initials: S
authors.lastname: Huang
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D053143:Caspase 2 / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D038941:Polypyrimidine Tract-Binding Protein / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D034741:RNA, Small Interfering; D038941:Polypyrimidine Tract-Binding Protein; D053143:Caspase 2