Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation
International Journal of Cancer, Volume 124, No. 8, Year 2009
Notification
URL copied to clipboard!
Description
The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin β1 (Kpnβ1) and Karyopherin α2 (Kpnα2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnβ1 and Kpnα2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnβ1 in cancer cells significantly reduced cell proliferation, while Kpnα2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnβ1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnβ1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnβ1 and Kpnα2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnβ1, not Kpnα2, induces cancer cell death, making Crm1 and Kpnb1 promising candidates as both biomarkers and potential anticancer therapeutic targets. © 2008 Wiley-Liss, Inc.
Authors & Co-Authors
van der Watt, Pauline J.
South Africa, Cape Town
Faculty of Health Sciences
Maske, Christopher P.
South Africa, Cape Town
Faculty of Health Sciences
Hendricks, Denver T.
South Africa, Cape Town
Faculty of Health Sciences
Parker, M. Iqbal
South Africa, Cape Town
Faculty of Health Sciences
South Africa, Cape Town
International Center for Genetic Engineering and Biotechnology Icgeb
Denny, Lynette A.
South Africa, Cape Town
Faculty of Health Sciences
Govender, Dhirendra A.
South Africa, Cape Town
Faculty of Health Sciences
Birrer, Michael J.
United States, Rockville
National Cancer Institute Nci
Leaner, Virna D.
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 246
Authors: 8
Affiliations: 3
Identifiers
Doi:
10.1002/ijc.24146
ISSN:
00207136
e-ISSN:
10970215
Research Areas
Cancer
Study Design
Cross Sectional Study
Study Approach
Quantitative