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Title: KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

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. - Highlights: • KPNA7 expression is elevated in several pancreaticmore » cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.« less
Authors:
;  [1] ;  [2] ; ;  [1] ;  [1] ;  [2]
  1. Institute of Biomedical Technology, FIN-33014 University of Tampere and BioMediTech, Biokatu 6, 33520 Tampere (Finland)
  2. (Finland)
Publication Date:
OSTI Identifier:
22395876
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 322; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; CELL CYCLE; HUMAN POPULATIONS; IN VITRO; INHIBITION; MESSENGER-RNA; MONOCLINIC LATTICES; MORTALITY; NEOPLASMS; PANCREAS; PHOSPHORUS 21; PLANT GROWTH; PLANT TISSUES; RECEPTORS; TRANSPORT