KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro
| Autor: | Hanna E. Rauhala, Elisa M. Vuorinen, Kimmo Savinainen, Anne Kallioniemi, Eeva Laurila |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
alpha Karyopherins medicine.medical_specialty Active Transport Cell Nucleus Receptors Cytoplasmic and Nuclear Biology Pancreatic cancer Internal medicine medicine Tumor Cells Cultured Gene silencing Humans RNA Small Interfering Receptor Karyopherin chemistry.chemical_classification Cell Nucleus Cell growth Autophagy Cell Biology Cell cycle medicine.disease Gene Expression Regulation Neoplastic Pancreatic Neoplasms medicine.anatomical_structure Endocrinology Cell Transformation Neoplastic chemistry Cancer research RNA Interference Pancreas |
| Zdroj: | Experimental cell research. 322(1) |
| ISSN: | 1090-2422 |
| Popis: | Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. |
| Databáze: | OpenAIRE |
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