Polo-like kinase 1
(PLK1) is a serine/threonine kinase that plays critical roles in cell cycling
and DNA damage response. Overexpression of PLK1 is associated with the poorer
prognosis of cancers, including colorectal cancer (CRC). Although the
downstream pathways of the overexpression that lead to oncogenesis have been
extensively studied, little is known about the factors that cause the overexpression
of PLK1 in CRC. DNA methylation was reported to be affecting the expression of
PLK1 in some cancers. This study aimed to investigate the contribution of
genetic mutation and DNA methylation of the PLK1 gene to the overexpression of
PLK1 in CRC.
The study involved data mining from Catalogue of Somatic Mutations in
Cancer (COSMIC) and UniProtKB, Sanger sequencing on DNA from the cell lines
HCT116, SW48, Colo320DM and T84 to analyze the possible mutation of PLK1. Other
than that methylation status of the PLK1 promoter in CRC were also analyzed by
using mass spectrometry (MS) and pyrosequencing. Data from the COSMIC showed
the low incidences of PLK1 mutation for CRC (3.02%) with 46 mutations
identified. One of the mutation p.R337Q (c.1010G > A) was located in the
D-box which was an important motif for protein ubiquitination and eventually
proteasomal degradation. Hence this mutation may potentially result in
stabilisation of the PLK1 protein. Mutations were detected at the upstream
silencer region, the promoter region and Exon1 in HCT116 but were not located
at the protein binding or functioning site. Similarly, the same mutation at
promoter region was detected in SW48. Differential trends of changes in
methylation status of PLK1 in the IR treated CRC cell lines detected by MS
revealed the possible association between the methylation and the
radiosensitivity. Furthermore, pyrosequencing showed that PLK1 methylation
status in tumor tissues with high expression of PLK1 was not significantly
different from those with no PLK1 expression.
In conclusion, mutation of PLK1 gene is infrequent in CRC and the
expression of PLK1 is unlikely to be dependent on DNA methylation in the
promoter region of PLK1 in the CRC.
Article
by Wayne Ng, et al, from Australia.
Full
access: http://mrw.so/1IhSr4
Image
by Digestive & Liver Disease Consultants, PA, from Flickr-cc.
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