Analysis of the candidate tumor suppressor Ris-1 in primary human breast carcinomas.
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.
Silva
Javier
J
Department of Medical Oncology, Hospital Universitario Puerta de Hierro, C/San Martín de Porres, E-28035 Madrid, Spain.
Silva
José M A
JM
Barradas
Marta
M
García
José M
JM
Domínguez
Gemma
G
García
Vanesa
V
Peña
Cristina
C
Gallego
Isabel
I
Espinosa
Ruth
R
Serrano
Manuel
M
Bonilla
Félix
F
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*
D008565:Membrane Proteins; C449281:TMEM158 protein, human; D025521:Tumor Suppressor Proteins