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Overexpression of nuclear protein kinase CK2 α catalytic subunit (CK2α) as a poor prognosticator in human colorectal cancer.

Lin KY, Tai C, Hsu JC, Li CF, Fang CL, Lai HC, Hseu YC, Lin YF, Uen YH - PLoS ONE (2011)

Bottom Line: Thus, novel therapeutic approaches are badly needed.We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients.The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α) in tumor progression, and in the prognosis of human CRC.

Methodology/principal findings: Expression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC) staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.

Conclusions/significance: Taken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC.

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Related in: MedlinePlus

Effect of CK2α gene silencing on colon cancer                            cell proliferation.Panel A. Nuclear CK2α expression in siRNA treated and                            un-treated DLD-1 colon cancer cells was examined by Western blot                            analysis. Panel B. Histograms representing the cell                            proliferation assay results based on the average of three independent                            experiments. *denotes P<0.001 compared with                            un-treated DLD-1 cells. Panel C. The representative                            photomicrographs.
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pone-0017193-g004: Effect of CK2α gene silencing on colon cancer cell proliferation.Panel A. Nuclear CK2α expression in siRNA treated and un-treated DLD-1 colon cancer cells was examined by Western blot analysis. Panel B. Histograms representing the cell proliferation assay results based on the average of three independent experiments. *denotes P<0.001 compared with un-treated DLD-1 cells. Panel C. The representative photomicrographs.

Mentions: To determine the effect of CK2α expression on DLD-1 human colon cancer cell proliferation, CK2α gene was knocked down by transfection of CK2α-specific siRNA. Scrambled siRNAs were used as controls. After CK2α-specific siRNA treatment, the expression level of nuclear CK2α in DLD-1 cells was significantly inhibited (Figure 4A). However, scrambled siRNA resulted in no significant inhibition (Figure 4A). We counted the number of colonies of siRNA-treated and un-treated DLD-1 cells. The colonies of CK2α-specific siRNA-treated cells were significantly fewer than those of un-treated and scrambled siRNA-treated cells (decreased to 33% (day 8) and 57% (day 14) of those of un-treated cells, respectively) (Figure 4B). The representative photomicrographs were shown in Figure 4C. The results indicated a role played by CK2α in promoting cell proliferation and is consistent with the clinical data described above.


Overexpression of nuclear protein kinase CK2 α catalytic subunit (CK2α) as a poor prognosticator in human colorectal cancer.

Lin KY, Tai C, Hsu JC, Li CF, Fang CL, Lai HC, Hseu YC, Lin YF, Uen YH - PLoS ONE (2011)

Effect of CK2α gene silencing on colon cancer                            cell proliferation.Panel A. Nuclear CK2α expression in siRNA treated and                            un-treated DLD-1 colon cancer cells was examined by Western blot                            analysis. Panel B. Histograms representing the cell                            proliferation assay results based on the average of three independent                            experiments. *denotes P<0.001 compared with                            un-treated DLD-1 cells. Panel C. The representative                            photomicrographs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040762&req=5

pone-0017193-g004: Effect of CK2α gene silencing on colon cancer cell proliferation.Panel A. Nuclear CK2α expression in siRNA treated and un-treated DLD-1 colon cancer cells was examined by Western blot analysis. Panel B. Histograms representing the cell proliferation assay results based on the average of three independent experiments. *denotes P<0.001 compared with un-treated DLD-1 cells. Panel C. The representative photomicrographs.
Mentions: To determine the effect of CK2α expression on DLD-1 human colon cancer cell proliferation, CK2α gene was knocked down by transfection of CK2α-specific siRNA. Scrambled siRNAs were used as controls. After CK2α-specific siRNA treatment, the expression level of nuclear CK2α in DLD-1 cells was significantly inhibited (Figure 4A). However, scrambled siRNA resulted in no significant inhibition (Figure 4A). We counted the number of colonies of siRNA-treated and un-treated DLD-1 cells. The colonies of CK2α-specific siRNA-treated cells were significantly fewer than those of un-treated and scrambled siRNA-treated cells (decreased to 33% (day 8) and 57% (day 14) of those of un-treated cells, respectively) (Figure 4B). The representative photomicrographs were shown in Figure 4C. The results indicated a role played by CK2α in promoting cell proliferation and is consistent with the clinical data described above.

Bottom Line: Thus, novel therapeutic approaches are badly needed.We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients.The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.

ABSTRACT

Background: Colorectal cancer (CRC) is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α) in tumor progression, and in the prognosis of human CRC.

Methodology/principal findings: Expression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC) staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition.

Conclusions/significance: Taken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC.

Show MeSH
Related in: MedlinePlus