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CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation
Judit Pallares1, David Llobet, Maria Santacana
1Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLLEIDA, Lleida, Spain.
Abstract:
Protein kinase CK2 (CK2) is a serine/threonine kinase that participates in important cellular processes. We have recently demonstrated that CK2 plays a role in resistance to TRAIL/Fas-induced apoptosis in endometrial carcinoma (EC) by regulating FLIP. Here, we assessed the immunohistochemical expression of CK2beta in EC and checked its role in cell proliferation and anchorage-independent cell growth. CK2beta immunostaining was assessed in two tissue microarrays, one constructed from paraffin-embedded blocks of 95 ECs and another from 70 samples of normal endometrium. CK2beta expression was correlated with histological type; grade and stage; cell proliferation (Ki-67) and apoptotic index; immunostaining for cyclin D1, PTEN, AKT, beta-catenin, and FLIP. Moreover, the Ishikawa EC cell line was subjected to down-regulation of CK2 by shRNA. CK2beta expression was frequent in EC (nuclear, 100%; cytoplasmic, 87.5%). The staining was more intense in EC than in normal endometrium (P = 0.000), and statistically correlated with AKT, PTEN, beta-catenin, and FLIP. In EC, CK2beta expression correlated with cell proliferation. Knock-down of CK2beta blocked colony formation of EC in soft agar, and also resulted in decreased expression of cyclin D1 and ERK phosphorylation. The results confirm that CK2beta is widely expressed in EC, and suggest a role in cell proliferation and anchorage-independent cell growth.
Insights
Protein kinase CK2 (CK2) is highly expressed in endometrial carcinoma (EC). This study found CK2beta promotes EC cell proliferation and anchorage-independent growth, suggesting it
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein kinase CK2 (CK2) is a serine/threonine kinase involved in crucial cellular functions.
- Previous research indicated CK2's role in TRAIL/Fas-induced apoptosis resistance in endometrial carcinoma (EC) via FLIP regulation.
Purpose of the Study:
- To investigate the immunohistochemical expression of CK2beta in EC.
- To determine the role of CK2beta in EC cell proliferation and anchorage-independent growth.
Main Methods:
- Immunohistochemical analysis of CK2beta expression in 95 EC tissues and 70 normal endometrium samples.
- Correlation analysis of CK2beta expression with clinicopathological features, proliferation markers (Ki-67), and other proteins (cyclin D1, PTEN, AKT, beta-catenin, FLIP).
- Down-regulation of CK2beta in Ishikawa EC cells using shRNA to assess effects on cell growth and protein expression.
Main Results:
- CK2beta was frequently expressed in EC (nuclear 100%, cytoplasmic 87.5%) with higher intensity than in normal endometrium.
- CK2beta expression correlated significantly with AKT, PTEN, beta-catenin, and FLIP.
- CK2beta expression correlated with increased cell proliferation in EC.
- CK2beta down-regulation inhibited EC colony formation in soft agar and reduced cyclin D1 expression and ERK phosphorylation.
Conclusions:
- CK2beta is widely expressed in endometrial carcinoma.
- CK2beta plays a significant role in promoting EC cell proliferation and anchorage-independent growth.
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