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Elevated expression of the nuclear export protein, Crm1 (exportin 1), associates with human oesophageal squamous cell carcinoma.
- Source :
-
Oncology reports [Oncol Rep] 2014 Aug; Vol. 32 (2), pp. 730-8. Date of Electronic Publication: 2014 Jun 04. - Publication Year :
- 2014
-
Abstract
- The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.
- Subjects :
- Adult
Aged
Antibiotics, Antineoplastic pharmacology
Carcinoma, Squamous Cell pathology
Cell Line, Tumor
Cell Nucleus metabolism
Cell Proliferation
Cytoplasm metabolism
Esophageal Neoplasms pathology
Esophageal Squamous Cell Carcinoma
Fatty Acids, Unsaturated pharmacology
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Exportin 1 Protein
Carcinoma, Squamous Cell metabolism
Esophageal Neoplasms metabolism
Karyopherins genetics
Karyopherins metabolism
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Cytoplasmic and Nuclear metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2431
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Oncology reports
- Publication Type :
- Academic Journal
- Accession number :
- 24898882
- Full Text :
- https://doi.org/10.3892/or.2014.3231