The Deficiency of Nuclear Proteins GATA6 and Lamin A/C as Prognostic Factor for Cervical Neoplasia

Callinice D. Capo-chichi^{1, 2,} , Blanche Aguida¹, Kathy Qi Cai³, Georges Offrin⁴, Vidéhouénou K Agossou⁵, Ambaliou Sanni¹ and Xiang-Xi Xu²

¹Institute of Biomedical Sciences and Applications (ISBA), Division of Molecular Biomarkers in Cancer and Nutrition (BMCN), Unit of Biochemistry and Molecular Biology (UBBM), Faculty of Sciences and Technologies (FAST), University Abomey-Calavi (UAC), Cotonou, BENIN

²Sylvester Cancer Center/ Miller School of Medicine, Department of Cell Biology, University of Miami, FL 33136, USA

³Fox Chase Cancer Center, Philadelphia, PA 19111, USA

⁴Hospital Mènontin, BP 160, Cotonou, BENIN

⁵National University Hospital (CNHU), Cotonou, BENIN

Cite this paper:
Callinice D. Capo-chichi, Blanche Aguida, Kathy Qi Cai, Georges Offrin, Vidéhouénou K Agossou, Ambaliou Sanni and Xiang-Xi Xu. The Deficiency of Nuclear Proteins GATA6 and Lamin A/C as Prognostic Factor for Cervical Neoplasia. American Journal of Cancer Prevention. 2015; 3(6):109-116. doi: 10.12691/ajcp-3-6-2

Abstract

BACKGROUND: Cervical cancer is a deadly disease for women worldwide and could be prevented if early molecular screening was performed ahead of cytology. In most neoplastic lesions the expression of nuclear proteins GATA6 and/or lamin A/C is deficient. OBJECTIVE: To analyze GATA6 and lamin A/C in archived cervical epithelial tissues and in cells derived from cervical uterine smears (CUS). METHODS: Immunofluorescence was used to analyze GATA6 and lamin A/C in epithelial cell lines. Immunohistochemistry was used to analyze GATA6 and lamin A/C expression in normal and neoplastic archived cervical tissues. Immunoblotting was used to analyze GATA6 and lamin A/C in cells of CUS obtained freshly from 40 selected women (age 20-45 years) who were attending routine gynecological checkup in Hospital Mènontin (Cotonou, BENIN). Colposcopy was used to visualize the vaginal tract and the uterine-cervix junction. This study is approved by our Institutional Research Ethic Committee and by the Ministry of Health in BENIN. RESULTS: Our data shows that the expression of GATA6 and lamin A/C is altered prior to cervical neoplastic lesions. The nuclear biomarkers GATA6 and lamin A/C are absent in 13% of CUS samples. Colposcopic examination performed after two years on 15 women lacking GATA6 and/or lamin A/C shows that 20% of them have developed cervical neoplastic lesions. CONCLUSION: These preliminary results suggest that the deficiency of GATA6 and lamin A/C in CUS could be used as biomarkers to contribute to the identification of women at risk of developing cervical lesions. However further studies are required for cancer prevention.

Keywords:
nuclear proteins GATA6 lamin A/C; cervical neoplasia cancer prevention

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Louie, K.S., Sanjose, S. and Mayaud P. Epidemiology and prevention of human papillomavirus and cervical cancer in sub-Saharan Africa: a comprehensive review. Trop Med Int Health, 14, 1287-1302, Oct 2009.
[2]	Bello, F.A., Enaboor, O.O. and Adewole, I.F. Human papilloma virus vaccination for control of cervical cancer: a challenge for developing countries. Afr J Reprod Health, 15, 25-30. Mar 2011.
[3]	Mitchell, S.M., Sekikubo, M., Biryabarema, C., Byamugisha, J.J., Steinberg, M., Jeronimo, J., Money, D.M., Christilaw, J. and Ogilvie, G.S. Factors associated with high-risk HPV positivity in a low-resource setting in sub-Saharan Africa. Am J Obstet Gynecol, 210 (1), 81.e1-7, Aug 2014.
[4]	Jaquet, A., Horo, A., Ekouevi, D.K., Toure, B., Coffie, P.A., Effi, B., Lenaud, S., Messou, E., Minga, A., Sasco, A.J. and Dabis, F. Risk Factors for Cervical Intraepithelial Neoplasia in HIV Infected Women on Antiretroviral Treatment in Côte d’Ivoire, West Africa. PLoS One, 9 (3), e90625, Mar 2014.
[5]	Capo-chichi, C.D., Roland, I.H., Vanderveer, L., Bao, R., Yamagata, T., Hirai, H., Cohen, C., Hamilton, T.C., Godwin, A.K. and Xu, X.X. Anomalous expression of epithelial differentiation-determining GATA factors in ovarian tumorigenesis. Cancer Res, 63(16), 4967-4977, Aug 2003.
[6]	Cai, K.Q., Caslini, C., Capo-chichi, C.D., Slater, C., Smith, E.R., Wu, H., Klein-Szanto, A.J., Godwin, A.K. and Xu, X.X. Loss of GATA4 and GATA6 expression specifies ovarian cancer histological subtypes and precedes neoplastic transformation of ovarian surface epithelia. PLoS One, 4(7):e6454, Jul 2009.
[7]	Capo-Chichi, C.D., Cai, K.Q., Testa, J.R., Godwin, A.K. and Xu, X.X. Loss of GATA6 Leads to Nuclear Deformation and Aneuploidy in Ovarian Cancer. Mol. Cell Biol, 29(17), 4766-4777, Sep 2009.
[8]	Capo-chichi, C.D., Cai, K.Q., Simpkins, F., Ganjei-Azar, P., Godwin, A.K. and Xu, X.X. Nuclear envelope structural defects cause chromosomal numerical instability and aneuploidy in ovarian cancer. BMC Med, 9, 28, Mar 2011.
[9]	Capo-Chichi, C.D., Cai, K.Q., Smedberg, J., Ganjei-Azar, P., Godwin, A.K. and Xu, X.X. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer. Chin J Cancer, (6):415-425, Jun 2011.
[10]	Capo-chichi, C.D., Alladagbin, J.D., Brun, L., Aguida, B., Agossou, K.V., Anagbla, T., Salmane, A., Xu, X.X. and Sanni, A. Deficiency of GATA6 as a Molecular Tool to Assess the Risk for Cervical Cancer. American Journal of Biomedical Research, 2 (1), 1-6, Jan 2014.
[11]	Capo-chichi, C.D., Rula, M.E., Smedberg, J.L., Vanderveer, L., Parmacek, M.S., Morrisey, E.E., Godwin, A.K. and Xu, X.X. Perception of differentiation cues by GATA factors in primitive endoderm lineage determination of mouse embryonic stem cells. Dev. Biol, 286(2), 574-586, Oct 2005.
[12]	Capo-chichi, C.D., Smedberg, J.L., Rula, M., Nicolas, E., Yeung, A.T., Adamo, R.F., Frolov, A., Godwin, A.K. and Xu, X.X. Alteration of Differentiation Potentials by Modulating GATA Transcription Factors in Murine Embryonic Stem Cells. Stem Cells Int, 11, 2010:602068, May 2010.
[13]	Caruso, R.A., Fedele, F., Consolo, P., Luigiano, C., Venuti, A. and Cavallari, V. Abnormal nuclear structures (micronuclei, nucleoplasmic bridges, and nuclear buds) in a pleomorphic giant cell carcinoma of the stomach. Ultrastruct Pathol, 32(1), 11-15. Jan-Feb 2008.
[14]	Butler, J.T., Hall, L.L., Smith, K.P. and Lawrence, J.B. Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells. J Cell Biochem, 107(4), 609-621, Jul 2009.
[15]	Capo-chichi CD, Smith ER, Rosario S, Ganjei-Azar P , Xu XX. Nuclear envelope defects in epithelial ovarian cancer. Am. J. Clin. Exp. Obstet. Gynecol, 1(1), 17-30, Dec 2013.
[16]	Corso, C., Parry, E.M., Faragher, R.G., Seager, A., Green, M.H. and Parry, J.M. Molecular cytogenetic insights into the ageing syndrome Hutchinson-Gilford Progeria (HGPS). Cytogenet Genome Res, 111(1), 27-33, 2005.
[17]	Capell, B.C. and Collins, F.S. Human laminopathies: nuclei gone genetically awry. Nat Rev Genet, 7(12), 940-952, Dec 2006. Review.
[18]	Ward, K.K, Berenson, A.B., and Breitkopf, C.R. Passive smoke exposure and abnormal cervical cytology in a predominantly Hispanic population. Am J Obstet Gynecol, 204(3):213 e1-6, Mar 2011.
[19]	Lazarenko, L.M., Nikitina, O.E., Nikitin, E.V., Demchenko, O.M., Kovtonyuk, G.V., Ganova, L.O., Bubnov, R.V., Shevchuk, V.O., Nastradina, N.M., Viktoria, V. V. and Spivak, M.Y. Development of biomarker panel to predict, prevent and create treatments tailored to the persons with human papillomavirus-induced cervical precancerous lesions. EPMA Journal, 5(1), Jan 2014.
[20]	Adam ML, Pini C, Túlio S, Cantalice JC, Torres RA, Correia MT. Assessment of the Association Between Micronuclei and the Degree of Uterine Lesions and Viral Load in Women with Human Papillomavirus. Cancer Genomics Proteomics, 12(2):67-71. Mar 2015.
[21]	Kivi, N., Greco, D., Auvinen, P., Auvinen, E. Genes involved in cell adhesion, cell motility and mitogenic signaling are altered due to HPV 16 E5 protein expression. Oncogene, 27(18):2532-2541. Apr 2008, Epub Nov 2007.
[22]	Caslini, C., Capo-chichi, C.D., Roland , I.H., Nicolas, E., Yeung, A.T., and Xu XX. Histone modifications silence the GATA transcription factor genes in ovarian cancer. Oncogene, 25(39), 5446-5461, Aug 2006.
[23]	Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimura, G., Kato, H. and Fukushima, Y. Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes. Am J Med Genet A, 143(21), 2598-2603, Nov 2007.
[24]	Somech, R., Shaklai, S., Amariglio, N., Rechavi, G. and Simon, A.J. Nuclear envelopathies--raising the nuclear veil. Pediatr Res, 57(5 Pt 2), 8R-15R, May 2005, Review.
[25]	Chaturvedi, P., Khanna, R., Parnaik,V.K. Ubiquitin ligase RNF123 Mediates Degradation of Heterochromatin Protein 1α and β in Lamin A/C Knock-Down Cells. Plos One, 7 (10) e47558, Oct 2012.
[26]	Shaklai, S., Amariglio, N., Rechav,i G. and Simon, A.J. Gene silencing at the nuclear periphery. FEBS J, 274(6), 1383-1392, Mar 2007. Review.
[27]	Hudon, S.E., Coffinier, C., Michaelis, S., Fong, L.G., Stephen, G., Young, S.G and Hrycyna, C,A. HIV-Protease Inhibitors Block the Enzymatic Activity of Purified Ste24p. Biochem Biophys Res Commun, 374(2), 365–368. Sep, 2008.
[28]	Zhou, J., Hernandez, G., Tu, S.W., Scholes, J., Chen, H., Tseng, C.P. and Hsieh, J.T. Synergistic induction of DOC-2/DAB2 gene expression in transitional cell carcinoma in the presence of GATA6 and histone deacetylase inhibitor. Cancer Res, 65(14), 6089-96, Jul 2005.
[29]	Venables, R.S., McLean, S., Luny, D., Moteleb, E., Morley, S. and Quinlan, R.A, Lane EB, Hutchison CJ. Expression of individual lamins in basal cell carcinomas of the skin. Br J Cancer, 84(4),512-519, Feb 2001.
[30]	Galiová, G., Bártová, E., Raska, I., Krejcí, J. and Kozubek, S. Chromatin changes induced by lamin A/C deficiency and the histone deacetylase inhibitor trichostatin A. Eur J Cell Biol, 87(5):291-303, May 2008.