Lamin A/C deficiency is an independent risk factor for cervical cancer

Callinice D. Capo-chichi, Blanche Aguida, Nicodème W. Chabi, Qi K. Cai, Georges Offrin, Vidéhouénou K. Agossou, Ambaliou Sanni, Xiangxi Xu

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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. Conclusion: Lamin A/C deficiency may serve as an independent risk factor for CIN development and as an indicator for preventive therapy in cervical cancer.

Original languageEnglish (US)
Pages (from-to)59-68
Number of pages10
JournalCellular Oncology
Volume39
Issue number1
DOIs
StatePublished - Feb 1 2016

Keywords

  • Cervical cancer prevention
  • Cervical neoplasia
  • Lamin A/C deficiency
  • Oncogenic HPV

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

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