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Molecular Medicine

, Volume 21, Issue 1, pp 167–179 | Cite as

Oncogenic Role of the Ec Peptide of the IGF-1Ec Isoform in Prostate Cancer

  • Athanasios Armakolas
  • Maria Kaparelou
  • Andreas Dimakakos
  • Efstathia Papageorgiou
  • Nikolaos Armakolas
  • Athanasios Antonopoulos
  • Constantina Petraki
  • Maria Lekarakou
  • Pavlos Lelovas
  • Martha Stathaki
  • Constantinos Psarros
  • Ismene Donta
  • Panos S. Galanos
  • Paul Msaouel
  • Vassilis G. Gorgoulis
  • Michael Koutsilieris
Research Article

Abstract

IGF-1 is one of the key molecules in cancer biology; however, little is known about the role of the preferential expression of the premature IGF-1 isoforms in prostate cancer. We have examined the role of the cleaved COO− terminal peptide (PEc) of the third IGF-1 isoform, IGF-1Ec, in prostate cancer. Our evidence suggests that endogenously produced PEc induces cellular proliferation in the human prostate cancer cells (PC-3) in vitro and in vivo, by activating the ERK1/2 pathway in an autocrine/paracrine manner. PEc overexpressing cells and tumors presented evidence of epithelial to mesenchymal transition, whereas the orthotopic injection of PEc-overexpressing, normal prostate epithelium cells (HPrEC) in SCID mice was associated with increased metastatic rate. In humans, the IGF-1Ec expression was detected in prostate cancer biopsies, where its expression correlates with tumor stage. Our data describes the action of PEc in prostate cancer biology and defines its potential role in tumor growth, progression and metastasis.

Notes

Acknowledgments

We thank Professors Hahn, Harvard Medical School, Boston, Massachusetts for the kind donation of the immortalized HPrEC cells and Kotsinas Athanasios, Consoulas Chris and Sideridou Maria and Chris Adamopoulos, from Athens Medical School, National and Kapodestrian University of Athens, for helpful discussions.

Supplementary material

10020_2015_2101167_MOESM1_ESM.pdf (1.9 mb)
Supplementary material, approximately 1.87 MB.

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© The Author(s) 2015

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Authors and Affiliations

  • Athanasios Armakolas
    • 1
  • Maria Kaparelou
    • 1
  • Andreas Dimakakos
    • 1
  • Efstathia Papageorgiou
    • 1
  • Nikolaos Armakolas
    • 2
  • Athanasios Antonopoulos
    • 2
  • Constantina Petraki
    • 3
  • Maria Lekarakou
    • 3
  • Pavlos Lelovas
    • 4
  • Martha Stathaki
    • 1
  • Constantinos Psarros
    • 1
  • Ismene Donta
    • 5
  • Panos S. Galanos
    • 6
  • Paul Msaouel
    • 1
  • Vassilis G. Gorgoulis
    • 6
    • 7
    • 8
    • 9
  • Michael Koutsilieris
    • 1
  1. 1.Physiology Laboratory, Medical SchoolNational and Kapodistrian University of AthensGoudi-AthensGreece
  2. 2.Third Orthopaedic ClinicKAT General HospitalAthensGreece
  3. 3.Department of PathologyMetropolitan General HospitalAthensGreece
  4. 4.Biomedical Research Foundation Academy of AthensCenter for Experimental SurgeryAthensGreece
  5. 5.Laboratory for Research of the Musculoskeletal System Theodoros GarofalidisUniversity of Athens, KAT Hospital KifisiaAthensGreece
  6. 6.Molecular Carcinogenesis Group, Laboratory of Histology and Embryology, Medical SchoolUniversity of AthensAthensGreece
  7. 7.Biomedical Research FoundationAcademy of AthensAthensGreece
  8. 8.Institute for Cancer SciencesUniversity of Manchester, Manchester Academic Health Science CentreManchesterUK
  9. 9.Manchester Centre for Cellular MetabolismUniversity of Manchester, Manchester Academic Health Science CentreManchesterUK

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