Callinice D Capo-chichi1,2,3, Blanche Aguida4, Nicodème W Chabi5, Qi K Cai6, Georges Offrin7, Vidéhouénou K Agossou8, Ambaliou Sanni9, Xiang-Xi Xu10. 1. 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. 2. National University Hospital (CNHU), Cotonou, BENIN. callinice.capochichi@gmail.com. 3. 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. 4. Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. aguiblanche@yahoo.fr. 5. Faculty of Sciences and Technology (FAST)/Institute of Biomedical Sciences and Applications (ISBA), University of Abomey-Calavi (UAC), Abomey Calavi, Benin. nicodchabi@yahoo.fr. 6. Fox Chase Cancer Center, Philadelphia, PA, 19111, USA. Qi.Cai@fccc.edu. 7. Hospital Mènontin, Cotonou, Benin. offringeorges@yahoo.fr. 8. National University Hospital (CNHU), Cotonou, BENIN. akomlanvidehouenou@gmail.com. 9. 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. 10. Sylvester Cancer Center/Miller Medical School of Medicine, University of Miami, Coral Gables, FL, USA. xxu2@med.miami.edu.
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.
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.
Authors: E Weiderpass; W Ye; R Tamimi; D Trichopolous; O Nyren; H Vainio; H O Adami Journal: Cancer Epidemiol Biomarkers Prev Date: 2001-08 Impact factor: 4.254
Authors: Brenda Y Hernandez; Katharine McDuffie; Lynne R Wilkens; Lori Kamemoto; Marc T Goodman Journal: Cancer Causes Control Date: 2003-11 Impact factor: 2.506
Authors: Qing-Yi Lu; Yanan Yang; Yu Sheng Jin; Zuo-Feng Zhang; David Heber; Frederick P Li; Steven M Dubinett; Melissa A Sondej; Joseph A Loo; Jian Yu Rao Journal: Proteomics Date: 2009-02 Impact factor: 3.984
Authors: Sarah E Hudon; Catherine Coffinier; Susan Michaelis; Loren G Fong; Stephen G Young; Christine A Hrycyna Journal: Biochem Biophys Res Commun Date: 2008-07-17 Impact factor: 3.575
Authors: Andrea Gingelmaier; Thomas Grubert; Ralph Kaestner; Ioannis Mylonas; Tobias Weissenbacher; Florian Bergauer; Lisa Barthell; Klaus Friese Journal: Anticancer Res Date: 2007 Jul-Aug Impact factor: 2.480
Authors: Ahmad Aljada; Joseph Doria; Ayman M Saleh; Shahad H Al-Matar; Sarah AlGabbani; Heba Bani Shamsa; Ahmad Al-Bawab; Altayeb Abdalla Ahmed Journal: Cell Oncol (Dordr) Date: 2016-01-05 Impact factor: 6.730
Authors: Elise Kaspi; Diane Frankel; Julien Guinde; Sophie Perrin; Sophie Laroumagne; Andrée Robaglia-Schlupp; Kevin Ostacolo; Karim Harhouri; Rachid Tazi-Mezalek; Joelle Micallef; Hervé Dutau; Pascale Tomasini; Annachiara De Sandre-Giovannoli; Nicolas Lévy; Pierre Cau; Philippe Astoul; Patrice Roll Journal: PLoS One Date: 2017-08-14 Impact factor: 3.240