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.
Highlights
The role of IGF-1 as a potent growth and survival factor in human cancer is long established
Our results suggest that PEc is a key molecule in tumor growth and survival and it is involved in the epithelial mesenchymal transition (EMT) phenomenon of prostate cancer cells leading to metastases
We selected the wild type PC-3 prostate cancer cell line that expresses only a minor amount of IGF-1Ec compared with LNCaP prostate cancer cells and to human prostate epithelial cells (HPrEc) under tissue culture conditions [5]
Summary
The role of IGF-1 as a potent growth and survival factor in human cancer is long established. Recent studies have suggested the preferential expression of the IGF-1Ec isoform in prostate cancer [5], whereas the exogenous administration of a synthetic 24-amino acid peptide of the COO– terminal of the Ec isoform (parts of exons 5 and 6 of the IGF-1 gene), has been associated with a statistically significant increase in proliferation in PC-3 and LNCaP prostate cancer cells [5]. The effects of this synthetic PEc have been proposed to be generated by extracellular signal-regulated kinase (ERK) but not Akt, promoting prostate cancer cell growth in vitro [5]. The role of Ec in cancer biology remains to be elucidated
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