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Expression and clinical significance of Wee1 in colorectal cancer

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Tumor Biology

Abstract

Wee1 is a nuclear kinase regulating cell cycle progression, and has emerged as a promising therapeutic target in cancer. Expression of Wee1 has been associated with poor outcome in certain tumor types, but the prognostic impact and clinical significance in colorectal cancer is unknown. The expression of Wee1 was examined by immunohistochemistry in primary colorectal carcinomas from a prospectively collected patient cohort, and associations with clinicopathological parameters and outcome were investigated. Cell culture experiments were performed using the cell lines RKO and SW620, and the relationship with the metastasis-promoting protein S100A4 was investigated. Nuclear expression was detected in 229 of the 258 tumors analyzed (89 %). Wee1 staining was associated with low pT stage, but no other significant associations with demographic or histopathological variables were found. Moderate Wee1 staining intensity was a predictor of favorable metastasis-free and overall survival compared to strong intensity and no or weak staining. The fraction of positive cells was not a prognostic factor in the present cohort. Inhibition of Wee1 expression using siRNA or treatment with the Wee1 inhibitor MK-1775 reduced expression of the metastasis-promoting protein S100A4, but no relationship between Wee1 and S100A4 was found in the patient samples. In conclusion, Wee1 is highly expressed in primary colorectal carcinomas, but few relevant associations with clinicopathological parameters or outcome were found. The lack of clinical significance of Wee1 expression could indicate that other tumor types might be better suited for further development of Wee1 inhibitors.

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Acknowledgments

We would like to thank Ellen Hellesylt for excellent technical assistance.

Author information

Authors and Affiliations

  1. Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, NO-0424, Oslo, Norway

    Eivind Valen Egeland, Kjersti Flatmark, Gunhild M. Mælandsmo & Kjetil Boye

  2. Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Kjersti Flatmark

  3. Medical Faculty, University of Oslo, Oslo, Norway

    Kjersti Flatmark & Jahn M. Nesland

  4. Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Jahn M. Nesland & Vivi Ann Flørenes

  5. Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

    Gunhild M. Mælandsmo

  6. Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway

    Kjetil Boye

Authors
  1. Eivind Valen Egeland
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  2. Kjersti Flatmark
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  6. Kjetil Boye
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Corresponding author

Correspondence to Kjetil Boye.

Ethics declarations

The study was approved by the Regional Ethics Committee (no. S-98080) and written informed consent was obtained from the patients.

Funding

This work was supported by the Norwegian Cancer Society (grant no. 4218523581 to E.V.E.) and the Research Council of Norway.

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None.

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Egeland, E.V., Flatmark, K., Nesland, J.M. et al. Expression and clinical significance of Wee1 in colorectal cancer. Tumor Biol. 37, 12133–12140 (2016). https://doi.org/10.1007/s13277-016-5081-3

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  • DOI: https://doi.org/10.1007/s13277-016-5081-3

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