Differential expression of genes involved in the epigenetic regulation of cell identity in normal human mammary cell commitment and differentiation
CHINESE JOURNAL OF CANCER
Authors: Coradini, Danila; Boracchi, Patrizia; Oriana, Saro; Biganzoli, Elia; Arnbrogi, Federico
Abstract
The establishment and maintenance of mammary epithelial cell identity depends on the activity of a group of proteins, collectively called maintenance proteins, that act as epigenetic regulators of gene transcription through DNA methylation, histone modification, and chromatin remodeling. Increasing evidence indicates that dysregulation of these crucial proteins may disrupt epithelial cell integrity and trigger breast tumor initiation. Therefore, we explored in silico the expression pattern of a panel of 369 genes known to be involved in the establishment and maintenance of epithelial cell identity and mammary gland remodeling in cell subpopulations isolated from normal human mammary tissue and selectively enriched in their content of bipotent progenitors, committed luminal progenitors, and differentiated myoepithelial or differentiated luminal cells. The results indicated that, compared to bipotent cells, differentiated myoepithelial and luminal subpopulations were both characterized by the differential expression of 4 genes involved in cell identity maintenance: CBX6 and PCGF2, encoding proteins belonging to the Polycomb group, and SMARCD3 and SMARCE1, encoding proteins belonging to the Trithorax group. In addition to these common genes, the myoepithelial phenotype was associated with the differential expression of HDAC1, which encodes histone deacetylase 1, whereas the luminal phenotype was associated with the differential expression of SMARCA4 and HAT1, which encode a Trithorax protein and histone acetylase 1, respectively. The luminal compartment was further characterized by the overexpression of ALDH1A3 and GATA3, and the down-regulation of NOTCH4 and CCNB1, with the latter suggesting a block in cell cycle progression at the G(2) phase. In contrast, myoepithelial differentiation was associated with the overexpression of MYC and the down-regulation of CCNE1, with the latter suggesting a block in cell cycle progression at the G(1) phase.
Preventing Progression of Fibrosis in Dupuytren's Contracture via Knockdown of Profibrotic Factors (CBX6 and CBX7): Pilot In Vitro Human Tissue Analysis
WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE
Authors: Oliver, Jeremie D.
Abstract
Objective. The purpose of this study is to investigate the efficacy of the knockdown of specific profibrotic factors (CBX6 and CBX7) as a potential technique to halt further fibroproliferative progression in human palmar fascia tissue affected by Dupuytren's contracture. Materials and Methods. A heat map was created based on genes of interest found to be upregulated in the diseased tissue as compared with normal palmar fascia tissue; CBX6 and CBX7 were identified. Knockdown of CBX6 and CBX7 was achieved by selective small interfering ribonucleic acid transfection. Results. Analysis of quantitative polymerase chain reaction data supported evidence of decreased collagen deposition in Alizarin Red stain in cultures having been transfected. Conclusions. The results of this study support the hypothesis that the process of fibrosis in Dupuytren's contracture potentially could be controlled via manipulation of epigenetic regulators.