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Published in: Medical Oncology 5/2017

01-05-2017 | Original Paper

Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma

Authors: Zhaofei Pang, Lixuan Cui, Nan Ding, Linhai Zhu, Xiao Qu, Wei Dong, Jiajun Du, Qi Liu

Published in: Medical Oncology | Issue 5/2017

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Abstract

IGF1R (insulin-like growth factor receptor-1) was confirmed to play a significant role in the development of cancer. Cezanne-1 overexpression was considered to be associated with enhancement of EGFR signaling pathway and reduced degeneration of EGFR. There was a close relationship between EGFR and IGFR as previous study showed. Dynamic balance between receptor ubiquitination and deubiquitination was critical in the process of termination of IGF signaling pathway. So we conducted an IHC staining to initially prove the correlation. Cezanne-1 and IGF1R expressions were evaluated in 103 patients with lung adenocarcinoma using immunohistochemical (IHC) analysis. The relationship between expressions of cezanne-1 and IGF1R were analyzed by χ2 test. Kaplan–Meier method was used to generate the survival curve, and the statistical difference was calculated by log-rank test. We also used data in R2 system to verify the relationship between IGF1R and cezanne-1. R2 system showed there was a close correlation between IGF1R and cezanne-1. Positive expression of cezanne-1 was detected in 64.1% patients. A significant association was shown between cezanne-1 and IGF1R expression (p < 0.001). Multivariate analysis confirmed that both cezanne-1 and IGF1R expressions were independent prognostic factors for OS. (HR 2.96, 95% CI 1.090–8.060, p = 0.033; HR 2.273, 95% CI 1.016–5.085, p = 0.046, respectively). Our findings indicated both cezanne-1 and IGF1R expressions were negative independent predictive factors for the prognosis of lung adenocarcinoma, respectively. There was a close positive interrelationship between cezanne-1 and IGF1R expression.
Literature
2.
go back to reference Pardee AB. G1 events and regulation of cell proliferation. Science (New York, NY). 1989;246(4930):603–8.CrossRef Pardee AB. G1 events and regulation of cell proliferation. Science (New York, NY). 1989;246(4930):603–8.CrossRef
3.
go back to reference Cross M, Dexter TM. Growth factors in development, transformation, and tumorigenesis. Cell. 1991;64(2):271–80.CrossRefPubMed Cross M, Dexter TM. Growth factors in development, transformation, and tumorigenesis. Cell. 1991;64(2):271–80.CrossRefPubMed
5.
6.
go back to reference Lee AV, Jackson JG, Gooch JL, Hilsenbeck SG, Coronado-Heinsohn E, Osborne CK et al. Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Molecular endocrinology (Baltimore, Md). 1999;13(5):787-96. doi:10.1210/mend.13.5.0274. Lee AV, Jackson JG, Gooch JL, Hilsenbeck SG, Coronado-Heinsohn E, Osborne CK et al. Enhancement of insulin-like growth factor signaling in human breast cancer: estrogen regulation of insulin receptor substrate-1 expression in vitro and in vivo. Molecular endocrinology (Baltimore, Md). 1999;13(5):787-96. doi:10.​1210/​mend.​13.​5.​0274.
8.
go back to reference Macaulay VM, Middleton MR, Protheroe AS, Tolcher A, Dieras V, Sessa C, et al. Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors. Ann Oncol. 2013;24(3):784–91. doi:10.1093/annonc/mds511.CrossRefPubMed Macaulay VM, Middleton MR, Protheroe AS, Tolcher A, Dieras V, Sessa C, et al. Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors. Ann Oncol. 2013;24(3):784–91. doi:10.​1093/​annonc/​mds511.CrossRefPubMed
10.
go back to reference Kim YH, Sumiyoshi S, Hashimoto S, Masago K, Togashi Y, Sakamori Y, et al. Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer. Clin Lung Cancer. 2012;13(5):385–90. doi:10.1016/j.cllc.2011.11.009.CrossRefPubMed Kim YH, Sumiyoshi S, Hashimoto S, Masago K, Togashi Y, Sakamori Y, et al. Expressions of insulin-like growth factor receptor-1 and insulin-like growth factor binding protein 3 in advanced non-small-cell lung cancer. Clin Lung Cancer. 2012;13(5):385–90. doi:10.​1016/​j.​cllc.​2011.​11.​009.CrossRefPubMed
12.
go back to reference Zhao S, Chen SS, Gu Y, Jiang EZ, Yu ZH. Expression and clinical significance of sushi domain- containing protein 3 (SUSD3) and Insulin-like growth factor-I receptor (IGF-IR) in breast cancer. Asian Pacific J Cancer Prev APJCP. 2015;16(18):8633–6.CrossRef Zhao S, Chen SS, Gu Y, Jiang EZ, Yu ZH. Expression and clinical significance of sushi domain- containing protein 3 (SUSD3) and Insulin-like growth factor-I receptor (IGF-IR) in breast cancer. Asian Pacific J Cancer Prev APJCP. 2015;16(18):8633–6.CrossRef
16.
go back to reference Worrall C, Nedelcu D, Serly J, Suleymanova N, Oprea I, Girnita A, et al. Novel mechanisms of regulation of IGF-1R action: functional and therapeutic implications. Pediatric Endocrinol Rev PER. 2013;10(4):473–84. Worrall C, Nedelcu D, Serly J, Suleymanova N, Oprea I, Girnita A, et al. Novel mechanisms of regulation of IGF-1R action: functional and therapeutic implications. Pediatric Endocrinol Rev PER. 2013;10(4):473–84.
17.
go back to reference Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111(6):1710–7.CrossRefPubMed Mountain CF. Revisions in the international system for staging lung cancer. Chest. 1997;111(6):1710–7.CrossRefPubMed
18.
go back to reference Yu J, Wang L, Zhang T, Shen H, Dong W, Ni Y, et al. Co-expression of beta-arrestin1 and NF-small ka, CyrillicB is associated with cancer progression and poor prognosis in lung adenocarcinoma. Tumour Biol. 2015;36(8):6551–8. doi:10.1007/s13277-015-3349-7.CrossRefPubMed Yu J, Wang L, Zhang T, Shen H, Dong W, Ni Y, et al. Co-expression of beta-arrestin1 and NF-small ka, CyrillicB is associated with cancer progression and poor prognosis in lung adenocarcinoma. Tumour Biol. 2015;36(8):6551–8. doi:10.​1007/​s13277-015-3349-7.CrossRefPubMed
19.
go back to reference Sehat B, Andersson S, Girnita L, Larsson O. Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis. Cancer Res. 2008;68(14):5669–77. doi:10.1158/0008-5472.can-07-6364.CrossRefPubMed Sehat B, Andersson S, Girnita L, Larsson O. Identification of c-Cbl as a new ligase for insulin-like growth factor-I receptor with distinct roles from Mdm2 in receptor ubiquitination and endocytosis. Cancer Res. 2008;68(14):5669–77. doi:10.​1158/​0008-5472.​can-07-6364.CrossRefPubMed
20.
go back to reference Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol. 2003;23(9):3363–72.CrossRefPubMedPubMedCentral Vecchione A, Marchese A, Henry P, Rotin D, Morrione A. The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and stability of the insulin-like growth factor I receptor. Mol Cell Biol. 2003;23(9):3363–72.CrossRefPubMedPubMedCentral
22.
go back to reference Prager D, Li HL, Yamasaki H, Melmed S. Human insulin-like growth factor I receptor internalization. Role of the juxtamembrane domain. J Biol Chem. 1994;269(16):11934–7.PubMed Prager D, Li HL, Yamasaki H, Melmed S. Human insulin-like growth factor I receptor internalization. Role of the juxtamembrane domain. J Biol Chem. 1994;269(16):11934–7.PubMed
26.
go back to reference Enesa K, Zakkar M, Chaudhury H, le Luong A, Rawlinson L, Mason JC, et al. NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem. 2008;283(11):7036–45. doi:10.1074/jbc.M708690200.CrossRefPubMed Enesa K, Zakkar M, Chaudhury H, le Luong A, Rawlinson L, Mason JC, et al. NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J Biol Chem. 2008;283(11):7036–45. doi:10.​1074/​jbc.​M708690200.CrossRefPubMed
27.
go back to reference Goetsch L, Gonzalez A, Leger O, Beck A, Pauwels PJ, Haeuw JF, et al. A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer. 2005;113(2):316–28. doi:10.1002/ijc.20543.CrossRefPubMed Goetsch L, Gonzalez A, Leger O, Beck A, Pauwels PJ, Haeuw JF, et al. A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer. 2005;113(2):316–28. doi:10.​1002/​ijc.​20543.CrossRefPubMed
Metadata
Title
Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma
Authors
Zhaofei Pang
Lixuan Cui
Nan Ding
Linhai Zhu
Xiao Qu
Wei Dong
Jiajun Du
Qi Liu
Publication date
01-05-2017
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2017
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-017-0934-1

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