Armakolas Athanasios, Kaparelou Maria, Dimakakos Andreas, Papageorgiou Efstathia, Armakolas Nikolaos, Antonopoulos Athanasios, Petraki Constantina, Lekarakou Maria, Lelovas Pavlos, Stathaki Martha, Psarros Constantinos, Donta Ismene, Galanos Panos S, Msaouel Paul, Gorgoulis Vassilis G, Koutsilieris Michael
Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, Goudi-Athens, Greece.
Third Orthopaedic Clinic, KAT General Hospital, Kifisia, Attiki, Greece.
Mol Med. 2015 Jan 6;21(1):167-79. doi: 10.2119/molmed.2014.00222.
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.
胰岛素样生长因子-1（IGF-1）是癌症生物学中的关键分子之一；然而，对于前列腺癌中过早出现的IGF-1亚型的优先表达作用知之甚少。我们研究了第三种IGF-1亚型IGF-1Ec的切割型羧基末端肽（PEc）在前列腺癌中的作用。我们的证据表明，内源性产生的PEc通过以自分泌/旁分泌方式激活ERK1/2途径，在体外和体内诱导人前列腺癌细胞（PC-3）的细胞增殖。过表达PEc的细胞和肿瘤呈现上皮-间质转化的证据，而在SCID小鼠中异位注射过表达PEc的正常前列腺上皮细胞（HPrEC）与转移率增加有关。在人类中，在前列腺癌活检中检测到IGF-1Ec表达，其表达与肿瘤分期相关。我们的数据描述了PEc在前列腺癌生物学中的作用，并确定了其在肿瘤生长、进展和转移中的潜在作用。
