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

Cellular Oncology volume 39, pages 59–68 (2016)Cite this article

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.

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Acknowledgments

We thank Dr. Toussain Anagbla and nurse Wanou Sylvia, Gynecology/obstetric service, Hospital Mènontin, Benin for sample collection and Sossah Hiffo Jonas, master student, for assistance in HPV genotyping. The rector of the University of Abomey-Calavi, Pr. Sinsin A. Brice (Benin) and all the members of his office are acknowledged for their constant encouragement and support for all our innovative projects towards cancer research in Benin. We also thank Toni Yeasky, research assistant at the Sylvester Cancer Center, Miller Medical School, University of Miami, Miami, USA for being in charge of studying the mouse model of lamin A/C deficiency. Dr. Elizabeth Smith, Dr. Robert Moore and Dr. Wensi Tao, Sylvester Cancer Center, Miller Medical School, University of Miami, Miami, FL, USA are acknowledged for their support. Special thanks go to Dr. Elizabeth Smith for editing this manuscript. We are especially grateful to Dr. Véronique Tognisode, obstetrician, gynecologist and Director of Clinic Houéyiho, for her excellent work during the colposcopic examination in her medical center (Cotonou, Benin).

Authors' contributions

  1. 1.

    CDC: Principal investigator who has designed and carried out the study on lamin A/C as bio-indicator to assess the risk of developing cervical cancer among African women.

  2. 2.

    AB: PhD student who is involved in sample collection and lamin A/C analysis by Western blotting.

  3. 3.

    CNW: Specialist of HPV genotyping who supervised the HPV genotyping in this study.

  4. 4.

    QKC: Pathologist who has performed the lamin A/C immunostaining on the tissue microarray.

  5. 5.

    GO: Director of Hospital Mènontin who has supervised the sample collection by gynecologist and nurses.

  6. 6.

    VKA: Obstetrician and gynecologist who has performed the colposcopic examinations, the cervical neoplastic diagnoses and treatment (Cotonou, Benin).

  7. 7.

    XX: Adviser in the study.

  8. 8.

    SA: Director of the laboratory of Biochemistry and Molecular Biology within the University of Abomey Calavi (UAC) in Benin, where the analyses were carried out. He has established the protocol for HPV genotyping.

ᅟ

Author information

Affiliations

  1. Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin

    Callinice D. Capo-chichi, Blanche Aguida, Nicodème W. Chabi & Ambaliou Sanni

  2. Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Qi K. Cai

  3. Hospital Mènontin, Cotonou, Benin

    Georges Offrin

  4. National University Hospital (CNHU), Cotonou, BENIN

    Callinice D. Capo-chichi & Vidéhouénou K. Agossou

  5. Sylvester Cancer Center/Miller Medical School of Medicine, University of Miami, Coral Gables, FL, USA

    Xiang-Xi Xu

  6. 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 D. Capo-chichi

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  1. Callinice D. Capo-chichi
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  2. Blanche Aguida
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  7. Ambaliou Sanni
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  8. Xiang-Xi Xu
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Corresponding author

Correspondence to Callinice D. Capo-chichi.

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Competing interest

The authors have no competing interests. This is exclusively a collaborative academic research project between researchers from the University of Abomey Calavi (UAC), Benin, the Fox Chase Cancer Center, Philadelphia, USA, the University of Miami, Miller school of Medicine, USA, and the medical doctors and gynecologists of the Hospital Mènontin, Benin.

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Capo-chichi, C.D., Aguida, B., Chabi, N.W. et al. Lamin A/C deficiency is an independent risk factor for cervical cancer. Cell Oncol. 39, 59–68 (2016). https://doi.org/10.1007/s13402-015-0252-6

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Keywords

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