Document Detail


Polo-like kinase 1 (Plk1) is expressed by cutaneous T-cell lymphomas (CTCLs), and its downregulation promotes cell cycle arrest and apoptosis.
MedLine Citation:
PMID:  21436619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Polo-like kinases are serine/threonine kinases crucial for mitosis and DNA integrity. Plk1, the most well studied member of this family, is upregulated in several cancers, as well as in dividing cells with peak expression during G2/M phase. Recently, employing lesional skin from patients with cutaneous T-cell lymphoma (CTCL), we showed that Plk1 was increased mainly in advanced lesions. In this study, employing western blot and quantitative RT-PCR analyses, we demonstrated that Plk1 was overexpressed in multiple CTCL cell lines (HH, Hut78, MyLa, SeAx and SZ4). Further, a genetic knockdown (by short hairpin RNA) or enzyme activity inhibition (via a small molecule inhibitor, GW843682X) was found to result in a decrease in cell growth, viability and proliferation. Plk1 inhibition in CTCL cells also resulted in: (1) increased G(2)/M phase cell cycle arrest, (2) alteration in key mitotic proteins, (3) apoptosis and (4) multiple mitotic errors. Given our findings, clinical trials of Plk1 inhibitors in CTCL may be a promising area for further translational investigation. We speculate that overexpression of Plk1 may prove to be relevant to the progression and prognosis of CTCL through its direct impact on the regulation of tumor cell proliferation and indirect influence on the acquisition of somatic mutations by proliferating tumor cells.
Authors:
Minakshi Nihal; Nathalie Stutz; Travis Schmit; Nihal Ahmad; Gary S Wood
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-04-15
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  10     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-22     Completed Date:  2011-08-31     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1303-11     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of Wisconsin School of Medicine and Public Health and Paul P. Carbone Comprehensive Cancer Center, Madison, WI, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects
Benzimidazoles / pharmacology*,  therapeutic use
Blotting, Western
Cell Culture Techniques
Cell Cycle / drug effects
Cell Cycle Proteins / antagonists & inhibitors*,  genetics,  metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Clinical Trials as Topic
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Lymphoma, T-Cell, Cutaneous / diagnosis,  drug therapy,  genetics,  metabolism*,  pathology
Prognosis
Protein Kinase Inhibitors / pharmacology*,  therapeutic use
Protein-Serine-Threonine Kinases / antagonists & inhibitors*,  genetics,  metabolism
Proto-Oncogene Proteins / antagonists & inhibitors*,  genetics,  metabolism
RNA, Small Interfering / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Skin Neoplasms / diagnosis,  drug therapy,  genetics,  metabolism*,  pathology
Thiophenes / pharmacology*,  therapeutic use
Tumor Markers, Biological / antagonists & inhibitors*,  genetics,  metabolism
Chemical
Reg. No./Substance:
0/5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-((2-(trifluoromethyl)benzyl)oxy)thiophene-2-carboxamide; 0/Benzimidazoles; 0/Cell Cycle Proteins; 0/Protein Kinase Inhibitors; 0/Proto-Oncogene Proteins; 0/RNA, Small Interfering; 0/Thiophenes; 0/Tumor Markers, Biological; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/polo-like kinase 1
Comments/Corrections
Comment In:
Cell Cycle. 2011 May 15;10(10):1523   [PMID:  21478668 ]
Cell Cycle. 2011 May 15;10(10):1526   [PMID:  21478673 ]

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