title: Analysis of the candidate tumor suppressor Ris-1 in primary human breast carcinomas.
abstract: Frequent chromosome 3 losses have been described in several tumors types, which strongly suggest the presence of one or several tumor suppressor genes. Recently, a novel candidate tumor suppressor gene termed Ris-1 (for Ras-induced senescence 1) has been identified at chromosomal position 3p21.3. Ris-1 has been proposed to participate in anti-tumor responses that resemble cellular senescence and that are elicited by oncogenes such as Ras. To analyze the role of Ris-1 as a putative tumor suppressor gene in human breast cancer, we have performed a real-time quantitative analysis of its mRNA expression in 60 patients. Moreover, we carried out a first approach to evaluate the most common inactivation mechanism that can affect expression levels of tumor suppressor genes (mutation, promoter hypermethylation and allelic losses). Furthermore, a correlation study between expression as well as inactivating mechanisms of Ris-1 and several clinico-pathological parameters of the tumors was designed, with the objective of appraising the prognostic value of Ris-1 status. Decreased expression of Ris-1 was observed in 23% of the cases and overexpressed Ris-1 was detected in 15% of the primary breast tumors. Our data showed high frequency of LOH (30%) at one of the markers used. Nevertheless, a polymorphism related with the expression levels was described. Statistically significant correlations were found between decreased Ris-1 expression and negative progesterone receptors, as well as between overexpressing Ris-1 tumors and high histological grade. Despite all these data, we conclude that the suggested role of Ris-1 as tumor suppressor gene is not evident, at least in breast cancer. Future and larger series studies in different tumor types are necessary to clarify Ris-1 function in human cancer.
authors.affiliation: Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/San Martín de Porres, E-28035 Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: José M A
authors.initials: JM
authors.lastname: Silva
authors.forename: Marta
authors.initials: M
authors.lastname: Barradas
authors.forename: José M
authors.initials: JM
authors.lastname: García
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
authors.forename: Vanesa
authors.initials: V
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Isabel
authors.initials: I
authors.lastname: Gallego
authors.forename: Ruth
authors.initials: R
authors.lastname: Espinosa
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008565:Membrane Proteins; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C449281:TMEM158 protein, human; D025521:Tumor Suppressor Proteins