title: Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro.
abstract: Human cellular apoptosis susceptibility (chromosomal segregation 1-like, CSE1L) gene plays a role in nuclear-to-cytoplasm transport and chromosome segregation during mitosis, cellular proliferation, and apoptosis. CSE1L is involved in colon carcinogenesis. CSE1L gene expression was assessed with three data sets using Affymetrix U133 + gene chips on normal human colonic mucosa (NR), adenomas (ADs), and colorectal carcinoma (CRC). CSE1L protein expression in CRC, AD, and NR from the same patients was measured by immunohistochemistry using a tissue microarray. We evaluated CSE1L expression in CRC cells (HCT116, SW480, and HT29) and its biological functions. CSE1L mRNA was significantly increased in all AD and CRC compared with NR (P < 0.001 and P = 0.02, respectivly). We observed a change in CSE1L staining intensity and cellular localization by immunohistochemistry. CSE1L was significantly increased during the transition from AD to CRC when compared with NR in a CRC tissue microarray (P = 0.01 and P < 0.001). HCT116, SW480, and HT29 cells also expressed CSE1L protein. CSE1L knockdown by shRNA inhibited protein, resulting in decreased cell proliferation, reduced colony formation in soft agar, and induction of apoptosis. CSE1L protein is expressed early and across all stages of CRC development. shRNA knockdown of CSE1L was associated with inhibition of tumorigenesis in CRC cells. CSE1L may represent a potential target for treatment of CRC.
authors: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Jose M
authors: JM
authors: Pimiento
authors: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Kevin G
authors: KG
authors: Neill
authors: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Evita
authors: E
authors: Henderson-Jackson
authors: Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Steven A
authors: SA
authors: Eschrich
authors: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Dung-Tsa
authors: DT
authors: Chen
authors: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Kazim
authors: K
authors: Husain
authors: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Department of Oncological Sciences, University of South Florida, Tampa, Florida.
authors: David
authors: D
authors: Shibata
authors: Department of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Department of Oncological Sciences, University of South Florida, Tampa, Florida; Department of Chemical Biology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: domenico.coppola@moffitt.org.
authors: Domenico
authors: D
authors: Coppola
authors: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Mokenge P
authors: MP
authors: Malafa
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D029563:Cellular Apoptosis Susceptibility Protein / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein