Loss of MTG16a (CBFA2T3), a novel rDNA repressor, leads to increased ribogenesis and disruption of breast acinar morphogenesis.
Human MTG16a (CBFA2T3), a chromatin repressor with nucleolar localization, was described to act as a suppressor of breast tumourigenesis. Here we show that MTG16a is a novel ribosomal gene repressor, which can counteract MYC-driven activation of ribosomal RNA (rRNA) transcription. We also show that either knocking down MTG16a by RNA interference, or sequestering MTG16a outside the nucleolus of human breast epithelial cells, hampers acinar morphogenesis concomitant with up-regulation of rRNA synthesis and increased ribogenesis. This is the first demonstration that loss of MTG16a function in the nucleolus of breast epithelial cells can induce morphological and molecular changes typical of breast cancer initiation.
Rossetti
Stefano
S
Cancer Genetics Program, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. stefano.rossetti@roswellpark.org
Hoogeveen
André T
AT
Esposito
Joseph
J
Sacchi
Nicoletta
N
D001940:Breast / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002466:Cell Nucleolus / Q000378:metabolism; D004275:DNA, Ribosomal / Q000096:biosynthesis / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009024:Morphogenesis; D009697:Nucleolus Organizer Region / Q000235:genetics; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C115744:CBFA2T3 protein, human; D004275:DNA, Ribosomal; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins