title: Identification of SEC62 as a potential marker for 3q amplification and cellular migration in dysplastic cervical lesions.
abstract: Chromosome 3 amplification affecting the 3q26 region is a common genomic alteration in cervical cancer, typically marking the transition of precancerous intraepithelial lesions to an invasive phenotype. Though potential 3q encoded target genes of this amplification have been identified, a functional correlation of potential oncogenic function is still missing. In this study, we investigated copy number changes and the expression level of SEC62 encoded at 3q26.2 as a new potential 3q oncogene in dysplastic cervical lesions and analyzed its role in cervical cancer cell biology.
  
  
  
  Expression levels of Sec62 and vimentin were analyzed in liquid based cytology specimens from 107 women with varying grades of cervical dysplasia ranging from normal cases to cancer by immunofluorescence cytology. Additionally, a subset of 20 representative cases was used for FISH analyses targeting SEC62. To further explore the functional role of Sec62 in cervical cancer, HeLa cells were transfected with a SEC62 plasmid or SEC62 siRNA and analyzed for their proliferation and migration potential using real-time monitoring and trans-well systems as well as changes in the expression of EMT markers.
  
  
  
  FISH analyses of the swabbed cells showed a rising number of SEC62 gains and amplifications correlating to the grade of dysplasia with the highest incidence in high grade squamous intraepithelial lesions and squamous cell carcinomas. When analyzing the expression level of Sec62 and vimentin, we found a gradually increasing expression level of both proteins according to the severity of the dysplasia. In functional analyses, SEC62 silencing inhibited and SEC62 overexpression stimulated the migration of HeLa cells with only marginal effects on cell proliferation, the expression level of EMT markers and the cytoskeleton structure.
  
  
  
  Our study suggests SEC62 as a target gene of 3q26 amplification and a stimulator of cellular migration in dysplastic cervical lesions. Hence, SEC62 could serve as a potential marker for 3q amplification, providing useful information about the dignity and biology of dysplastic cervical lesions.
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, Building 6, 66421, Homburg/Saar, Germany. maximilian.linxweiler@uks.eu.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Linxweiler
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, Building 6, 66421, Homburg/Saar, Germany.|Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Kirrberger Street 100, Building 44, Homburg/Saar, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Bochen
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, Building 6, 66421, Homburg/Saar, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schick
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, Building 6, 66421, Homburg/Saar, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Wemmert
authors.affiliation: Department of Otorhinolaryngology, Saarland University Medical Center, Kirrberger Street 100, Building 6, 66421, Homburg/Saar, Germany.
authors.forename: Basel
authors.initials: B
authors.lastname: Al Kadah
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Saarland University Medical Center, Kirrberger Street 100, Building 44, Homburg/Saar, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Greiner
authors.affiliation: Department of General and Surgical Pathology, Saarland University Medical Center, Kirrberger Street 100, Building 26, Homburg/Saar, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hasenfus
authors.affiliation: Department of General and Surgical Pathology, Saarland University Medical Center, Kirrberger Street 100, Building 26, Homburg/Saar, Germany.
authors.forename: Rainer-Maria
authors.initials: RM
authors.lastname: Bohle
authors.affiliation: Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrberger Street 100, Building 9, Homburg/Saar, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Juhasz-Böss
authors.affiliation: Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrberger Street 100, Building 9, Homburg/Saar, Germany.
authors.forename: Erich-Franz
authors.initials: EF
authors.lastname: Solomayer
authors.affiliation: Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrberger Street 100, Building 9, Homburg/Saar, Germany.
authors.forename: Zoltan Ferenc
authors.initials: ZF
authors.lastname: Takacs
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D026901:Membrane Transport Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics / Q000473:pathology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D026901:Membrane Transport Proteins; C103676:SEC62 protein, human
keywords: 3q amplification; Cell migration; Cervical dysplasia; Epithelial-mesenchymal transition; SEC62