HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Combined expression levels of KDM2A and KDM2B correlate with nucleolar size and prognosis in primary breast carcinomas

Igor De Nicola1, Ania Naila Guerrieri2,3, Marianna Penzo2,3, Claudio Ceccarelli2, Antonio De Leo2,4, Davide Trerč2 and Lorenzo Montanaro2,3

1S. Orsola-Malpighi Hospital, University of Bologna, 2Department of Experimental, Diagnostic and Specialty medicine (DIMES), Alma Mater Studiorum - University of Bologna, 3Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum-University of Bologna and 4Pathology Unit, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

Offprint requests to: Lorenzo Montanaro, Center for Applied Biomedical Research (CRBA), Alma Mater Studiorum - University of Bologna, Italy. e-mail: lorenzo.montanaro@unibo.it


Summary. Ribosome biogenesis is a fine-tuned cellular process and its deregulation is linked to cancer progression: tumors characterized by an intense ribosome biogenesis often display a more aggressive behavior. Ribosomal RNA (rRNA) synthesis is controlled at several levels, the higher one being the epigenetic regulation of the condensation of chromatin portions containing rRNA genes. KDM2A and KDM2B (Lysine (K)-specific demethylase 2A/B) are histone demethylases modulating the accessibility of ribosomal genes, thereby regulating their transcription. Both enzymes are able to demethylate lysins at relevant sites (e.g. K4, K36) on histone H3. We previously demonstrated that KDM2B is one of the factors regulating ribosome biogenesis in human breast cancer. In this study we aimed to define the combined contribution of KDM2A and KDM2B to breast cancer outcome. KDM2A and KDM2B mRNA levels, nucleolar area as a marker of ribosome biogenesis, and patients' prognosis were retrospectively assessed in a series of primary breast carcinomas. We observed that tumors characterized by reduced levels of both KDM2A and KDM2B displayed a particularly aggressive clinical behavior and increased nucleolar size. Our results suggest that KDM2A and KDM2B may cooperate in regulating ribosome biogenesis thus influencing the biological behavior and clinical outcome of human breast cancers. Histol Histopathol 35, 1181-1187 (2020)

Key words: Breast Cancer, Histone modification, Ribosome biogenesis, Prognosis

DOI: 10.14670/HH-18-248