Regulation of LCoR and RIP140 expression in cervical intraepithelial neoplasia and correlation with CIN progression and dedifferentiation
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Authors: Vogelsang, Tilman L. R.; Schmoeckel, Elisa; Kuhn, Christina; Blankenstein, Thomas; Temelkov, Mina; Heidegger, Helene; Kolben, Theresa Maria; Kolben, Thomas; Mahner, Sven; Mayr, Doris; Jeschke, Udo; Vattai, Aurelia
Abstract
Purpose Ligand-dependent corepressor (LCoR) and receptor-interacting protein 140 (RIP140/NRIP1) play an important role in the regulation of multiple oncogenic signaling pathways and the development of cancer. LCoR and RIP140 form a nuclear complex in breast cancer cells and are of prognostic value in further prostate and cervical cancer. The purpose of this study was to analyze the regulation of these proteins in the development of cervical intraepithelial neoplasia (CIN I-III). Methods Immunohistochemical analysis was obtained to quantify RIP140 and LCoR expression in formalin-fixed paraffin embedded tissue sections of cervical intraepithelial neoplasia samples. Tissue (n = 94) was collected from patients treated in the Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich, Germany, between 2002 and 2014. Correlations of expression levels with clinical outcome were carried out to assess for prognostic relevance in patients with CIN2 progression. Kruskal-Wallis test and Mann-Whitney U test were used for data analysis. Results Nuclear LCoR overexpression correlates significantly with CIN II progression. Nuclear RIP140 expression significantly increases and nuclear LCoR expression decreases with higher grading of cervical intraepithelial neoplasia. Cytoplasmic RIP140 expression is significantly higher in CIN III than in CIN I or CIN II. Conclusion A decrease of nuclear LCoR expression in line with an increase of dedifferentiation of CIN can be observed. Nuclear LCoR overexpression correlates with CIN II progression indicating a prognostic value of LCoR in cervical intraepithelial neoplasia. Nuclear and cytoplasmic RIP140 expression increases significantly with higher grading of cervical intraepithelial neoplasia underlining its potential role in the development of pre-cancerous lesions. These findings support the relevance of LCoR and RIP140 in the tumorigenesis indicating a possible role of LCoR and RIP140 as targets for novel therapeutic approaches in cervical intraepithelial neoplasia and cervical cancer.
The electronic structure of (diiminopyridine)cobalt(I) complexes
EUROPEAN JOURNAL OF INORGANIC CHEMISTRY
Authors: Knijnenburg, Q; Hetterscheid, D; Kooistra, TM; Budzelaar, PHM
Abstract
DFT calculations show that square-planar (LCoR)-R-I complexes of a diiminopyridine ligand are best regarded as containing low-spin Co-II antiferromagnetically coupled to a ligand radical anion. The lowest triplet state, corresponding to a 3d(z)(2)-->pi* excitation, is calculated to be only a few kcal/mol above the ground state, and is thermally accessible. The anomalous H-1 NMR chemical shifts of the LCoR complexes are suggested to be due to thermal population of the triplet state at room temperature. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.