title: PTB-associated splicing factor (PSF) is a PPARγ-binding protein and growth regulator of colon cancer cells.
abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that plays an essential role in cell proliferation, apoptosis, and inflammation. It is over-expressed in many types of cancer, including colon, stomach, breast, and lung cancer, suggesting that regulation of PPARγ might affect cancer pathogenesis. Here, using a proteomic approach, we identify PTB-associated splicing factor (PSF) as a novel PPARγ-interacting protein and demonstrate that PSF is involved in several important regulatory steps of colon cancer cell proliferation. To investigate the relationship between PSF and PPARγ in colon cancer, we evaluated the effects of PSF expression in DLD-1 and HT-29 colon cancer cell lines, which express low and high levels of PPARγ, respectively PSF affected the ability of PPARγ to bind, and expression of PSF siRNA significantly suppressed the proliferation of colon cancer cells. Furthermore, PSF knockdown induced apoptosis via activation of caspase-3. Interestingly, DLD-1 cells were more susceptible to PSF knockdown-induced cell death than HT-29 cells. Our data suggest that PSF is an important regulator of cell death that plays critical roles in the survival and growth of colon cancer cells. The PSF-PPARγ axis may play a role in the control of colorectal carcinogenesis. Taken together, this study is the first to describe the effects of PSF on cell proliferation, tumor growth, and cell signaling associated with PPARγ.
authors.affiliation: Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, Asahi, Matsumoto, Nagano, Japan. ttamotsu@shinshu-u.ac.jp
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Hisao
authors.initials: H
authors.lastname: Haniu
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D019073:HT29 Cells; D006801:Humans; D047495:PPAR gamma / Q000378:metabolism*; D000072670:PTB-Associated Splicing Factor; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D000072670:PTB-Associated Splicing Factor; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins