Abstract
Interphase chromosomes have been shown to occupy discrete regions of the nucleus denominated chromosome territories (CTs), their active genes being preferentially positioned on the surfaces of these CTs, where they are accessible to transcriptional machinery. By means of FISH (Fluorescence in situ Hybridization), we analyzed the CCND1 and HER-2/neu gene positions within the CTs and their relationship with gene amplification and protein over-expression in esophageal and gastric cancers. The CCND1 and HER-2/Neu genes were more often positioned at the periphery (mean frequency of 60%-83%) of the CTs in tumor tissues of the esophagus and stomach. Moreover, this positioning revealed no association with either gene amplification or the protein over-expression status of these genes, although, in esophageal carcinoma, Kappa statistics showed a moderate agreement between amplification of the CCND1 gene (Kappa = 0.400) and its location within the CT, as well as with over-expression of the corresponding protein (Kappa = 0.444). Thus, our results suggest that gene positioning in interphase chromosomes does not follow a definitive pattern neither does it depend only on gene transcriptional activity. Apparently, this positioning could be both gene- and tissue-specific, and depends on other factors acting together, such as dense-gene, chromosome size, chromatin structure, and the level and stability of its expression.
Highlights
Studies focusing on the molecular components of DNA replication, transcription, RNA processing, DNA repair and the nuclear matrix (Berezney et al, 1995; Lamond and Earnshaw, 1998) have demonstrated that the interphase nucleus is structurally and functionally compartmentalized into regions that contain factors involved in RNA synthesis, processing and transport (Park and De Boni, 1998)
Chromosomes have been shown to maintain their identity during the entire cell cycle with moderate movement during the interphase (Zink et al, 1998), occupying discrete, non-overlapping regions of the nuclear volume called chromosome territories (CTs) or chromosome domains (CDs) (Cremer et al, 1993; Visser and Aten, 1999)
Given the controversy arising from positioning active transcriptional sequences in the periphery of chromosome territories, the aims of the present study were to evaluate spatial intranuclear distribution of CCND1 and HER-2/neu oncogenes within their respective chromosome 11 and 17 territories in esophageal carcinoma, gastric adenocarcinoma and normal mucosae, and to correlate the results so obtained with the gene amplification and protein overexpression status of both the CCND1 and Her-2/neu genes
Summary
Studies focusing on the molecular components of DNA replication, transcription, RNA processing, DNA repair and the nuclear matrix (Berezney et al, 1995; Lamond and Earnshaw, 1998) have demonstrated that the interphase nucleus is structurally and functionally compartmentalized into regions that contain factors involved in RNA synthesis, processing and transport (Park and De Boni, 1998). Kurz et al (1996) were the first to demonstrate that in muscle cells, fibroblasts and HeLa cells, the DMD, HBB and MYH7 genes (but not non-coding regions) are preferentially located in the periphery of their respective CTs, regardless of their activity. Extending this analysis, other studies have reported the preferential positioning of different genes in the periphery of the CTs in certain cell types, with or without association with transcriptional activity (Dietzel et al, 1999; Volpi et al, 2000; Galiová et al, 2004; Scheuermann et al, 2004; Harnicarová et al, 2006). C-myc transcripts associated with the site of synthesis are located more peripherally
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
