title: Lamin A/C deficiency is an independent risk factor for cervical cancer.
abstract: BACKGROUND
  In the past, cervical cancer has been linked to Human Papilloma Virus (HPV) infection. Previously, we found that pre-neoplastic breast and ovarian lesions may be associated with lamin A/C deficiency, resulting in abnormal nuclear morphologies and chromosomal instability. Ultimately, these phenomena are thought to lead to cancer. Here, we assessed lamin A/C deficiency as an indicator for the risk to develop cervical cancer.
  
  
  METHODS
  The expression of lamin A/C was assessed by Western blotting in cervical uterine smears (CUS) of 76 adult women from Benin concomitant with nuclear morphology assessment and HPV genotyping using microscopy and PCR-based assays, respectively. In vitro analyses were performed to uncover the mechanism underlying lamin A/C expression alterations observed in vivo. The presence of cervical intra-epithelial neoplasia (CIN) was assessed by colposcopy.
  
  
  RESULTS
  Normal lamin A/C expression (group A) was observed in 39% of the CUS, weak lamin A/C expression (group B) was observed in 28% of the CUS and no lamin A/C expression (group C) was observed in 33% of the CUS tested. Infection with oncogenic HPV was found to be significantly higher in group C (36%) than in groups A (17%) and B (14%). Two years after our first assessment, CIN was observed in 20% of the women in group C. The in vitro application of either a histone deacetylase inhibitor (trichostatin) or a protein kinase inhibitor (staurosporine) was found to restore lamin A/C expression in cervical cancer-derived cells.
  
  
  CONCLUSIONS
  Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer.
authors.affiliation: Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. callinice.capochichi@gmail.com.|National University Hospital (CNHU), Cotonou, BENIN. callinice.capochichi@gmail.com.|Unit of Biochemistry and Molecular Biology (UBBM), Section of Molecular Biomarkers in Cancer and Nutrition (BMCN), Faculty of Sciences and Technology (FAST), Institute of Biomedical Sciences and Applications (ISBA), University Abomey-Calavi (UAC), 04BP488, Cotonou, Benin. callinice.capochichi@gmail.com.
authors.forename: Callinice D
authors.initials: CD
authors.lastname: Capo-chichi
authors.affiliation: Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. aguiblanche@yahoo.fr.
authors.forename: Blanche
authors.initials: B
authors.lastname: Aguida
authors.affiliation: Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. nicodchabi@yahoo.fr.
authors.forename: Nicodème W
authors.initials: NW
authors.lastname: Chabi
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Qi.Cai@fccc.edu.
authors.forename: Qi K
authors.initials: QK
authors.lastname: Cai
authors.affiliation: Hospital Mènontin, Cotonou, Benin. offringeorges@yahoo.fr.
authors.forename: Georges
authors.initials: G
authors.lastname: Offrin
authors.affiliation: National University Hospital (CNHU), Cotonou, BENIN. akomlanvidehouenou@gmail.com.
authors.forename: Vidéhouénou K
authors.initials: VK
authors.lastname: Agossou
authors.affiliation: Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. ambaliou.sanni@fast.uac.bj.
authors.forename: Ambaliou
authors.initials: A
authors.lastname: Sanni
authors.affiliation: Sylvester Cancer Center/Miller Medical School of Medicine, University of Miami, Coral Gables, FL, USA. xxu2@med.miami.edu.
authors.forename: Xiang-Xi
authors.initials: XX
authors.lastname: Xu
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D053144:Cell Nucleus Shape; D003127:Colposcopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D034904:Lamin Type A / Q000172:deficiency* / Q000378:metabolism; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology; D014626:Vaginal Smears; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology
chemical_list: D034904:Lamin Type A; C440308:lamin C
keywords: Cervical cancer prevention; Cervical neoplasia; Lamin A/C deficiency; Oncogenic HPV