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Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation

Oncogene volume 22, pages 6013–6022 (2003)Cite this article

Abstract

The adenomatous polyposis coli (APC) tumor suppressor is a nucleocytoplasmic protein. The nuclear accumulation of APC was recently found to vary depending on cell density, suggesting that putative APC function(s) in the nucleus is controlled by the establishment of cell contacts. We report here that the density-dependent redistribution of APC between nucleus and cytoplasm prevails in 6/6 thyroid and colorectal carcinoma cell lines. Moreover, mutated APC lacking known nuclear localization sequences had the similar distribution pattern as the full-length protein. APC invariably accumulated in the nuclei of Ki-67 expressing cells, but was largely cytoplasmic when cell cycle exit was induced by serum starvation or at high cell density. APC colocalized with β-catenin in the nucleus only in one cell line (SW480). Also, APC maintained a predominantly nuclear position in early confluent states when cytoplasmic β-catenin was recruited to newly formed adherens-like junctions. The results indicate that nuclear targeting of APC is driven by cell cycle entry rather than altered cell–cell contact. The ability of C-terminally truncated APC to accumulate in the nucleus suggests that nuclear import signals other than NLS1APC and NLS2APC are functionally important. Residual function(s) of N-terminal APC fragments in tumor cells carrying APC mutations might be beneficial to tumor growth and survival.

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Acknowledgements

We are grateful to Dr Inke Näthke, Dundee, UK for generously sharing the APC antiserum, Dr Nils-Erik Heldin for providing the cell lines, Professor Keiko Funa for sharing FACS equipment, Mats Grände and other members of the Nilsson/Ericson lab for valuable discussions and to Therese Carlsson for technical assistance. This work was supported by grants from The Swedish Research Council (12X-537), The Assar Gabrielsson Foundation for Clinical Research, The Magnus Bergwall Foundation and by The Royal Swedish Academy of Sciences.

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, Göteborg University, Box 420, Göteborg, SE-40530, Sweden

    Henrik Fagman, Fredrik Larsson, Yvonne Arvidsson & Mikael Nilsson

  2. Department of Clinical Genetics, Göteborg University, Sahlgrenska University Hospital East, Göteborg, SE-41685, Sweden

    Johan Meuller, Margareta Nordling & Tommy Martinsson

  3. Department of Clinical Endocrinology, Medizinische Hochschule Hannover, Hannover, D-30625, Germany

    Karen Helmbrecht & Georg Brabant

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  1. Henrik Fagman
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Correspondence to Henrik Fagman.

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Fagman, H., Larsson, F., Arvidsson, Y. et al. Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation. Oncogene 22, 6013–6022 (2003). https://doi.org/10.1038/sj.onc.1206731

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