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

2.50
Hdl Handle:
http://hdl.handle.net/10541/92932
Title:
The human ROX gene: genomic structure and mutation analysis in human breast tumors.
Authors:
Lo Nigro, C; Venesio, T; Reymond, A; Meroni, G; Alberici, P; Cainarca, S; Enrico, F; Stack, Maria; Ledbetter, D H; Liscia, D S; Ballabio, A; Carrozzo, R
Abstract:
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.
Affiliation:
Telethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milan, Italy.
Citation:
The human ROX gene: genomic structure and mutation analysis in human breast tumors. 1998, 49 (2):275-82 Genomics
Journal:
Genomics
Issue Date:
15-Apr-1998
URI:
http://hdl.handle.net/10541/92932
DOI:
10.1006/geno.1998.5241
PubMed ID:
9598315
Type:
Article
Language:
en
ISSN:
0888-7543
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLo Nigro, Cen
dc.contributor.authorVenesio, Ten
dc.contributor.authorReymond, Aen
dc.contributor.authorMeroni, Gen
dc.contributor.authorAlberici, Pen
dc.contributor.authorCainarca, Sen
dc.contributor.authorEnrico, Fen
dc.contributor.authorStack, Mariaen
dc.contributor.authorLedbetter, D Hen
dc.contributor.authorLiscia, D Sen
dc.contributor.authorBallabio, Aen
dc.contributor.authorCarrozzo, Ren
dc.date.accessioned2010-02-24T14:04:23Z-
dc.date.available2010-02-24T14:04:23Z-
dc.date.issued1998-04-15-
dc.identifier.citationThe human ROX gene: genomic structure and mutation analysis in human breast tumors. 1998, 49 (2):275-82 Genomicsen
dc.identifier.issn0888-7543-
dc.identifier.pmid9598315-
dc.identifier.doi10.1006/geno.1998.5241-
dc.identifier.urihttp://hdl.handle.net/10541/92932-
dc.description.abstractWe 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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshBasic Helix-Loop-Helix Leucine Zipper Transcription Factors-
dc.subject.meshBreast Neoplasms-
dc.subject.meshCell Line-
dc.subject.meshChromosomes, Human, Pair 17-
dc.subject.meshDNA Mutational Analysis-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshExons-
dc.subject.meshHelix-Loop-Helix Motifs-
dc.subject.meshHumans-
dc.subject.meshIntrons-
dc.subject.meshLeucine Zippers-
dc.subject.meshLoss of Heterozygosity-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMutagenesis, Site-Directed-
dc.subject.meshRepressor Proteins-
dc.subject.meshTranscription Factors-
dc.titleThe human ROX gene: genomic structure and mutation analysis in human breast tumors.en
dc.typeArticleen
dc.contributor.departmentTelethon Institute of Genetics and Medicine (TIGEM), San Raffaele Biomedical Science Park, Milan, Italy.en
dc.identifier.journalGenomicsen

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