The human ROX gene: genomic structure and mutation analysis in human breast tumors.

Détails

ID Serval
serval:BIB_0D7BB4C8AA57
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
The human ROX gene: genomic structure and mutation analysis in human breast tumors.
Périodique
Genomics
Auteur⸱e⸱s
Lo Nigro C., Venesio T., Reymond A., Meroni G., Alberici P., Cainarca S., Enrico F., Stack M., Ledbetter D.H., Liscia D.S., Ballabio A., Carrozzo R.
ISSN
0888-7543 (Print)
ISSN-L
0888-7543
Statut éditorial
Publié
Date de publication
1998
Volume
49
Numéro
2
Pages
275-282
Langue
anglais
Résumé
We have recently isolated a human gene, ROX, encoding a new member of the basic helix-loop-helix leucine zipper protein family. ROX is capable of heterodimerizing with Max and acts as a transcriptional repressor in an E-box-driven reporter gene system, while it was found to activate transcription in HeLa cells. ROX expression levels vary during the cell cycle, being down-regulated in proliferating cells. These biological properties of ROX suggest a possible involvement of this gene in cell proliferation and differentiation. The ROX gene maps to chromosome 17p13.3, a region frequently deleted in human malignancies. Here we report the genomic structure of the human ROX gene, which is composed of six exons and spans a genomic region of less than 40 kb. In an attempt to identify possible inactivating mutations in the ROX gene in human breast cancer, we performed a single-strand conformation polymorphism analysis of its coding region in 16 sporadic breast carcinomas showing loss of heterozygosity in the 17p13.3 region. No mutations were found in this analysis. Five nucleotide polymorphisms were identified in the ROX gene, three of which caused an amino acid substitution. These nucleotide changes were present in the peripheral blood DNAs of both the patients and the control individuals. In vitro translated assays did not show a significant decrease in the ability of the ROX mutant proteins to bind DNA or to repress transcription of a driven reporter gene in HEK293 cells. Despite experimental evidence that ROX might act as a tumor suppressor gene, our data suggest that mutations in the coding region of ROX are uncommon in human breast tumorigenesis.
Mots-clé
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Breast Neoplasms/genetics, Cell Line, Chromosomes, Human, Pair 17/genetics, DNA Mutational Analysis, DNA-Binding Proteins/metabolism, Exons, Helix-Loop-Helix Motifs/genetics, Humans, Introns, Leucine Zippers/genetics, Loss of Heterozygosity/genetics, Molecular Sequence Data, Mutagenesis, Site-Directed, Repressor Proteins/genetics, Repressor Proteins/metabolism, Transcription Factors/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 15:51
Dernière modification de la notice
20/08/2019 12:34
Données d'usage