(SENCOL; 2007-2010); Principal Investigator Gabriela Anton, PhD)
Aim: The aim of this research project is to decode the cellular/molecular basis of regression for some high – grade HPV- induced lesions (CIN), and to understand the mechanisms which govern the biological systems for the optimization of the cancer prognostic. The specific objectives are:
(1) to create an experimental model in order to induce the senescence/ apoptosis process (through molecular and genetic engineering techniques) in viral transformed cell line cultures
(2) to identify, using microarray techniques, the gene clusters implicated in regression
(3) to validate the cellular pathways involved in regression related to the apoptosis/senescence process (using tissue microarray techniques from patients with severe dysplasia).
Partners: Coordinator: “Stefan S. Nicolau” Institute of Virology Bucharest– project director, Gabriela Anton, PhD.
Partner 1 – “Grigore T Popa” University of Medicine and Pharmacy Iasy, responsible Demetra Socolov, PhD
Partner 2 – Fundeni Clinical Institute, Bucharest, responsible Prf Irinel Popescu
Partner 3 -“Carol Davila” University of Medicine and Pharmacy, Bucharest, responsible Camil Bohiltea PhD
Funding: IVN = 900 000 LEI
Working team: Anton G, Brasoveanu L, Zaharia C, Stoian M, Antipa C, Plesa A, Bleotu C, Chivu M, Alexiu I, Grancea C, Botezatu A, Goia C, Iancu I.
Project financed by PC 4.1.1. contract no 41-030
Implementation period: 18.09.2007-18.09.2010
Summary: The activity developed in the partnership of this frame project, proposes to realize and consolidate an integrated research network. The domain of interest is to define and to identify the cellular pathways contributing to the regression of severe uterine cervix lesions, and to translate the results into clinical practice. This proposal belongs to the 4.1.1 direction – the development of the biological human systems knowledge.
HPV persistent infections represent the main, but not the sufficient cause for the development of most squamous cervix carcinomas and intermediate conditions like cervical intraepithelial neoplasia (CIN). In most immunocompetent women, CIN 1 lesions regress without any medical procedure. A small fraction of these lesions progresses to CIN2/3 dysplasia and lead to transformation. However, many authors report spontaneous regression in this type of cases in a percent of 6 – 50%. The mechanism through this intraepithelial lesions HPV- associated regress is not yet completely understood. The regression of the severe dysplasia is a complex phenomenon, determined through apoptotic and senescence pathways. It is clearly that the accelerated proliferation is insufficient for carcinogenesis and the proliferative cells need to elude the apoptosis and senescence process in order to manifest the malignant phenotype. In exchange, the spontaneous regression is characterized by the loss of the malignant phenotype, so the tumor cells will be the target of the apoptosis process. Like apoptosis, the senescence is a stress responsive mechanism, but instead of leading to cellular death, it stops the cellular proliferation.
Results:
1. Gabriela Anton, Demetra Socolov, Anca Botezatu, Cristina Goia, Marina Anton, Anca Stanescu, Adriana Pleşa, S Teleman, Human papillomavirus DNA and mRNA- markers for cervical lesions progression, Third International Congress of Molecular Medicine, May 5-8, 2009, Istanbul, Turkey, Abstract publicat în IUBMB Life, 2009, 61, 344, ISSN 1521-6543. IF= 3.5
2. Cristina Goia, Anca Botezatu, Demetra Socolov, Iulia. Iancu, Irina Huica, Adriana Plesa, Gabriela Anton, The implication of mtDNA mutations in HPV-induced cervical cancer, 35th FEBS Congress (Molecules of Life), 26 June-1 July 2010, Gothenburg, Sweden, FEBS Journal, 277 (suppl. 1), Abstract book pag. 91-92; ISSN: 1742-4658. IF=3.13
3. Iulia Iancu, Demetra Socolov, Anca Botezatu, Adriana Plesa, Carmen Ungureanu, Cristina Goia, Gabriela Anton, Expression of TGF-beta/Smads signaling in human cervical cancers, 35th FEBS Congress (Molecules of Life), 26 June-1 July 2010, Gothenburg, Sweden, FEBS Journal, 277 (suppl. 1), Abstract book p. 124-125; ISSN: 1742-4658. IF=3.13
