Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro

Jose M. Pimiento, Kevin G. Neill, Evita Henderson-Jackson, Steven A. Eschrich, Dung Tsa Chen, Kazim Husain, David Shibata, Domenico Coppola, Mokenge P. Malafa

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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.

Original languageEnglish (US)
Pages (from-to)2761-2768
Number of pages8
JournalAmerican Journal of Pathology
Volume186
Issue number10
DOIs
StatePublished - Oct 1 2016

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Colorectal Neoplasms
Carcinogenesis
Genes
Adenoma
HCT116 Cells
HT29 Cells
Apoptosis
Small Interfering RNA
Proteins
Immunohistochemistry
Cell Proliferation
Chromosome Segregation
Oligonucleotide Array Sequence Analysis
Mitosis
Agar
Colon
Cytoplasm
Mucous Membrane
Staining and Labeling
Gene Expression

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Pimiento, J. M., Neill, K. G., Henderson-Jackson, E., Eschrich, S. A., Chen, D. T., Husain, K., ... Malafa, M. P. (2016). Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro. American Journal of Pathology, 186(10), 2761-2768. https://doi.org/10.1016/j.ajpath.2016.06.016

Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro. / Pimiento, Jose M.; Neill, Kevin G.; Henderson-Jackson, Evita; Eschrich, Steven A.; Chen, Dung Tsa; Husain, Kazim; Shibata, David; Coppola, Domenico; Malafa, Mokenge P.

In: American Journal of Pathology, Vol. 186, No. 10, 01.10.2016, p. 2761-2768.

Research output: Contribution to journalArticle

Pimiento, JM, Neill, KG, Henderson-Jackson, E, Eschrich, SA, Chen, DT, Husain, K, Shibata, D, Coppola, D & Malafa, MP 2016, 'Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro', American Journal of Pathology, vol. 186, no. 10, pp. 2761-2768. https://doi.org/10.1016/j.ajpath.2016.06.016
Pimiento JM, Neill KG, Henderson-Jackson E, Eschrich SA, Chen DT, Husain K et al. Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro. American Journal of Pathology. 2016 Oct 1;186(10):2761-2768. https://doi.org/10.1016/j.ajpath.2016.06.016
Pimiento, Jose M. ; Neill, Kevin G. ; Henderson-Jackson, Evita ; Eschrich, Steven A. ; Chen, Dung Tsa ; Husain, Kazim ; Shibata, David ; Coppola, Domenico ; Malafa, Mokenge P. / Knockdown of CSE1L Gene in Colorectal Cancer Reduces Tumorigenesis in Vitro. In: American Journal of Pathology. 2016 ; Vol. 186, No. 10. pp. 2761-2768.
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