The human ROX gene

Genomic structure and mutation analysis in human breast tumors

Cristiana Lo Nigro, Tiziana Venesio, Alexandre Reymond, Germana Meroni, Paola Alberici, Silvia Cainarca, Fiorenza Enrico, Maria Stack, David H. Ledbetter, Daniel S. Liscia, Andrea Ballabio, Romeo Carrozzo

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)275-282
Number of pages8
JournalGenomics
Volume49
Issue number2
DOIs
Publication statusPublished - Apr 15 1998

Fingerprint

Breast Neoplasms
Mutation
Genes
Reporter Genes
Nucleotides
Leucine Zippers
HEK293 Cells
Loss of Heterozygosity
DNA
Mutant Proteins
Amino Acid Substitution
Tumor Suppressor Genes
HeLa Cells
Cell Differentiation
Exons
Cell Cycle
Carcinogenesis
Breast
Chromosomes
Cell Proliferation

ASJC Scopus subject areas

  • Genetics

Cite this

Nigro, C. L., Venesio, T., Reymond, A., Meroni, G., Alberici, P., Cainarca, S., ... Carrozzo, R. (1998). The human ROX gene: Genomic structure and mutation analysis in human breast tumors. Genomics, 49(2), 275-282. https://doi.org/10.1006/geno.1998.5241

The human ROX gene : Genomic structure and mutation analysis in human breast tumors. / Nigro, Cristiana Lo; Venesio, Tiziana; Reymond, Alexandre; Meroni, Germana; Alberici, Paola; Cainarca, Silvia; Enrico, Fiorenza; Stack, Maria; Ledbetter, David H.; Liscia, Daniel S.; Ballabio, Andrea; Carrozzo, Romeo.

In: Genomics, Vol. 49, No. 2, 15.04.1998, p. 275-282.

Research output: Contribution to journalArticle

Nigro, CL, Venesio, T, Reymond, A, Meroni, G, Alberici, P, Cainarca, S, Enrico, F, Stack, M, Ledbetter, DH, Liscia, DS, Ballabio, A & Carrozzo, R 1998, 'The human ROX gene: Genomic structure and mutation analysis in human breast tumors', Genomics, vol. 49, no. 2, pp. 275-282. https://doi.org/10.1006/geno.1998.5241
Nigro, Cristiana Lo ; Venesio, Tiziana ; Reymond, Alexandre ; Meroni, Germana ; Alberici, Paola ; Cainarca, Silvia ; Enrico, Fiorenza ; Stack, Maria ; Ledbetter, David H. ; Liscia, Daniel S. ; Ballabio, Andrea ; Carrozzo, Romeo. / The human ROX gene : Genomic structure and mutation analysis in human breast tumors. In: Genomics. 1998 ; Vol. 49, No. 2. pp. 275-282.
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