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

Handle URI:
http://hdl.handle.net/10754/621435
Title:
Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells
Authors:
Moritz, Tom; Venz, Simone; Junker, Heike; Kreuz, Sarah; Walther, Reinhard; Zimmermann, Uwe
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Moritz T, Venz S, Junker H, Kreuz S, Walther R, et al. (2016) Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells. Tumor Biology 37: 10435–10446. Available: http://dx.doi.org/10.1007/s13277-016-4925-1.
Publisher:
Springer Nature
Journal:
Tumor Biology
Issue Date:
5-Feb-2016
DOI:
10.1007/s13277-016-4925-1
Type:
Article
ISSN:
1010-4283; 1423-0380
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorMoritz, Tomen
dc.contributor.authorVenz, Simoneen
dc.contributor.authorJunker, Heikeen
dc.contributor.authorKreuz, Sarahen
dc.contributor.authorWalther, Reinharden
dc.contributor.authorZimmermann, Uween
dc.date.accessioned2016-11-03T08:29:15Z-
dc.date.available2016-11-03T08:29:15Z-
dc.date.issued2016-02-05en
dc.identifier.citationMoritz T, Venz S, Junker H, Kreuz S, Walther R, et al. (2016) Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells. Tumor Biology 37: 10435–10446. Available: http://dx.doi.org/10.1007/s13277-016-4925-1.en
dc.identifier.issn1010-4283en
dc.identifier.issn1423-0380en
dc.identifier.doi10.1007/s13277-016-4925-1en
dc.identifier.urihttp://hdl.handle.net/10754/621435-
dc.description.abstractThe 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.en
dc.publisherSpringer Natureen
dc.subjectLNCaPen
dc.subjectNeuroendocrine transdifferentiationen
dc.subjectPC-1en
dc.subjectPrLZen
dc.subjectProstate canceren
dc.subjectTPD52en
dc.titleIsoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cellsen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalTumor Biologyen
dc.contributor.institutionDepartment of Medical Biochemistry and Molecular Biology, Ernst Moritz Arndt University of Greifswald, Ferdinand-Sauerbruch-Straße, Greifswald, Germanyen
dc.contributor.institutionDepartment of Urology, Ernst Moritz Arndt University Greifswald, Greifswald, Germanyen
kaust.authorKreuz, Sarahen
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