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Tumor Biology

, Volume 37, Issue 8, pp 10435–10446 | Cite as

Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

  • Tom Moritz
  • Simone Venz
  • Heike Junker
  • Sarah Kreuz
  • Reinhard Walther
  • Uwe Zimmermann
Original Article

Abstract

The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

Keywords

PC-1 PrLZ TPD52 Neuroendocrine transdifferentiation Prostate cancer LNCaP 

Notes

Acknowledgement

We thank Robert Beyer and Sina Holstein for their contribution on experimental work. Special thanks go to Prof. Dr. Nicole Endlich (Department of Anatomy and Cell Biology, University Medicine Greifswald) for the opportunity to use microscopes for live cell imaging.

Compliance with Ethical Standards

The manuscript does not contain clinical studies, animal studies or patient data.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Medical Biochemistry and Molecular BiologyErnst Moritz Arndt University of GreifswaldGreifswaldGermany
  2. 2.Laboratory of Chromatin Biochemistry, BESE DivisionKing Abdullah University of Science and TechnologyThuwalSaudi Arabia
  3. 3.Department of UrologyErnst Moritz Arndt University GreifswaldGreifswaldGermany

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