TY - JOUR
T1 - Polo-like kinase 1 (Plk1) is expressed by cutaneous T-cell lymphomas (CTCLs) and its downregulation promotes cell cycle arrest and apoptosis
AU - Nihal, Minakshi
AU - Stutz, Nathalie
AU - Schmit, Travis
AU - Ahmad, Nihal
AU - Wood, Gary S.
N1 - Funding Information:
This material is based on work supported by the Department of Veterans Affairs, Office of Research and Development, Biomedical Laboratory Research and Development Service. The contents do not represent the views of the Deptartment of Veterans Affairs or the U.S. Government.
PY - 2011/4/15
Y1 - 2011/4/15
N2 - 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 G 2/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 G2/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.
AB - 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 G 2/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 G2/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.
UR - http://www.scopus.com/inward/record.url?scp=79954498856&partnerID=8YFLogxK
U2 - 10.4161/cc.10.8.15353
DO - 10.4161/cc.10.8.15353
M3 - Journal articles
AN - SCOPUS:79954498856
SN - 1538-4101
VL - 10
SP - 1303
EP - 1311
JO - Cell Cycle
JF - Cell Cycle
IS - 8
ER -