@article{3001246,
    title = "Cervical cancer cell line secretome highlights the roles of transforming growth factor-beta-induced protein ig-h3, peroxiredoxin-2, and NRF2 on cervical carcinogenesis",
    author = "Kontostathi, G. and Zoidakis, J. and Makridakis, M. and Lygirou, V. and Mermelekas, G. and Papadopoulos, T. and Vougas, K. and Vlamis-Gardikas, A. and Drakakis, P. and Loutradis, D. and Vlahou, A. and Anagnou, N.P. and Pappa, K.I.",
    journal = "BioMed Research International",
    year = "2017",
    volume = "2017",
    publisher = "Hindawi Limited",
    issn = "2314-6133, 2314-6141",
    doi = "10.1155/2017/4180703",
    keywords = "alpha enolase;  calreticulin;  carboxypeptidase H;  cathepsin B;  cathepsin D;  follistatin related protein;  follistatin related protein 4;  fructose bisphosphate aldolase;  fructose bisphosphate aldolase a;  gelsolin;  glutathione transferase;  glutathione transferase p;  glyceraldehyde 3 phosphate dehydrogenase;  metalloproteinase inhibitor;  metalloproteinase inhibitor 1;  peroxiredoxin 2;  phosphoglycerate mutase;  phosphoglycerate mutase 1;  protein;  protein disulfide isomerase;  protein disulfide isomerase a3;  protein ig h3;  pyruvate kinase;  pyruvate kinase pkm;  Rho guanine nucleotide dissociation inhibitor 1;  transcription factor Nrf2;  transforming growth factor beta;  triosephosphate isomerase;  tripeptidyl peptidase I;  unclassified drug;  upstream stimulatory factor;  betaIG-H3 protein;  NFE2L2 protein, human;  peptide;  peroxiredoxin;  PRDX2 protein, human;  scleroprotein;  transcription factor Nrf2;  transforming growth factor beta, Article;  bioinformatics;  cancer cell;  carcinogenesis;  cervical carcinogenesis;  comparative study;  controlled study;  female;  human;  human cell;  matrix assisted laser desorption ionization time of flight mass spectrometry;  multiple reaction monitoring;  oxidative stress;  protein analysis;  protein expression;  protein function;  protein secretion;  proteomics;  quantitative analysis;  two dimensional gel electrophoresis;  upregulation;  uterine cervix cancer;  validation study;  Western blotting;  algorithm;  biology;  carcinogenesis;  chemistry;  complication;  gene expression regulation;  HeLa cell line;  Human papillomavirus type 16;  matrix-assisted laser desorption-ionization mass spectrometry;  metabolism;  papillomavirus infection;  proteomics;  signal transduction;  tandem mass spectrometry;  tumor cell line;  uterine cervix tumor, Algorithms;  Carcinogenesis;  Cell Line, Tumor;  Computational Biology;  Electrophoresis, Gel, Two-Dimensional;  Extracellular Matrix Proteins;  Female;  Gene Expression Regulation, Neoplastic;  HeLa Cells;  Human papillomavirus 16;  Humans;  NF-E2-Related Factor 2;  Papillomavirus Infections;  Peptides;  Peroxiredoxins;  Proteomics;  Signal Transduction;  Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;  Tandem Mass Spectrometry;  Transforming Growth Factor beta;  Uterine Cervical Neoplasms",
    abstract = "Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV-), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis. © 2017 Georgia Kontostathi et al."
}