RESUMEN
Methylation of arginine residues has been implicated in many cellular activities like mRNA splicing, transcription regulation, signal transduction and protein-protein interactions. Protein arginine methyltransferases are the enzymes responsible for this modification in living cells. The most commonly used methyltransferase in man is protein arginine methyltransferase 1 (PRMT1). Since methylation processes appear to interfere in the emergence of several diseases, including cancer, we investigated the localisation of the protein in cancer tissue and, for the first time, the relation that possibly exists between the expression of PRMT1 gene and breast cancer progression. We used tumour specimens from 62 breast cancer patients and semi-quantitative RT-PCR to determine the expression of PRMT1 gene and was found to be associated with patient's age (p = 0.002), menopausal status (p = 0.006), tumour grade (p = 0.03), and progesterone receptor status (p = 0.001). Survival curves revealed that PRMT1-v1 status-low expression relates to longer disease-free survival (DFS; p = 0.036). To the contrary, PRMT1-v2 status is not associated neither with the clinical or pathological parameters nor with DFS (p = 0.31). PRMT1-v3 was not statistically significantly expressed in breast cancer tissue. Selected cancer and normal breast samples were stained for PRMT1. In both normal and cancerous breast tissues, staining was in the cytoplasm and only in rare cases the cell nucleus appeared stained. Present results show a potential use for this gene as a marker of unfavourable prognosis for breast cancer patients.
Asunto(s)
Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Represoras/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Proteína-Arginina N-Metiltransferasas/análisis , Proteína-Arginina N-Metiltransferasas/fisiología , Proteínas Represoras/análisis , Proteínas Represoras/fisiologíaRESUMEN
Human tissue kallikrein-related peptidases are a family of 15 secreted serine proteases, located at chromosome 19q13.4. Most of them have been reported to be potential biomarkers for several carcinomas and other diseases. Human tissue kallikrein-related peptidase 7 (KLK7) has been purified from human stratum corneum and resembles a chymotryptic endopeptidase originally called stratum corneum chymotryptic enzyme (SCCE). In this study, we examined for the first time, the prognostic value of KLK7 mRNA expression, using a semi-quantitative RT-PCR method, in 105 colorectal cancer tissues for 54 of which, paired normal colonic mucosa were available. Furthermore, we analysed the expression of KLK7 in 10 adenomas, in 18 biopsies of inflamed colon mucosa, as well as in 22 human cancer cell lines of various origin, four of them being of colon. A defined number of colon cancer samples were also examined by immunohistochemistry. KLK7 expression was higher in cancerous than in normal tissues. Less differentiated tumors of more advanced stage showed higher KLK7 expression. Follow-up analysis revealed that KLK7 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). In addition, selected colon cancer samples highly expressing KLK7 gene, showed intense immunohistochemical staining for KLK7, enhancing RT-PCR results. Present data suggest that KLK7 gene is up-regulated in colon cancer and its expression predicts poor prognosis for colon cancer patients.
Asunto(s)
Adenoma/enzimología , Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/enzimología , Calicreínas/análisis , Adenoma/genética , Adenoma/mortalidad , Adenoma/patología , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Colitis/enzimología , Colitis/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Células HT29 , Humanos , Inmunohistoquímica , Mucosa Intestinal/enzimología , Calicreínas/genética , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
BACKGROUND: In this study, the possible relation of the expression pattern of arginine methyltransferase 1 and colon cancer progression is investigated. MATERIALS AND METHODS: Colon cancer samples as well as normal colon samples were used to define the arginine methyltransferase 1 expression by RT-PCR. The results were associated with clinical and histological parameters of the tissues. RESULTS: In colon cancer tissue, only PRMT1 variants v1 and v2 were often expressed. Statistical significance for the clinicopathological parameters examined was found only for PRMT1 variant v2. PRMT1 v2 expression was associated with nodal status and tumour grade. PRMT1 v2 expression analysis in 25 pairs of cancerous/non-cancerous colon tissue showed higher or equal expression in cancer versus normal tissue. In 18 inflamed colon tissues examined for PRMT1 expression and compared with the expression of 90 colon cancer tissue samples, statistical significance was found only for variants v1 and v2. A higher percentage of PRMT1 v2 expression was observed in older patients. CONCLUSION: From the present preliminary results, it can be said that PRMT1 variant v2 can probably be regarded as a marker of unfavourable prognosis in colon cancer patients.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Represoras/genética , Adulto , Anciano , Anciano de 80 o más Años , Empalme Alternativo , Biomarcadores de Tumor/metabolismo , Colon/enzimología , Colon/patología , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Proteína-Arginina N-Metiltransferasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Apoptosis is an active process regulated by a variety of genes. Recently, the molecular cloning, physical mapping and expression analysis of a novel gene of the Bcl-2 family, BCL2L12, was reported. Expression analysis of the BCL2L12 gene in breast cancer confirmed an association of BCL2L12 with favorable prognosis of patients. In the present study, the expression of the BCL2L12 gene was analyzed in colon cancer by RT-PCR. Two transcripts, BCL2L12 and BCL2L12-A, were overexpressed in the cancer tissues as compared to their paired normal mucosa. An association was found between BCL2L12-A transcript expression and nodal status, as well as Dukes' stage. The BCL2L12-A transcript appears to be of importance for colon cancer since its expression is associated with disease progression.
Asunto(s)
Apoptosis/fisiología , Neoplasias del Colon/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Proteínas Musculares/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Colon/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Marcadores Genéticos/genética , Marcadores Genéticos/fisiología , Humanos , Persona de Mediana Edad , Proteínas Musculares/genética , Modelos de Riesgos Proporcionales , Isoformas de Proteínas/biosíntesis , Isoformas de Proteínas/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Estadísticas no ParamétricasRESUMEN
SR (serine-arginine) proteins are essential pre-mRNA splicing factors. Several SR proteins have been characterized in humans, among them SR-A1. It has been demonstrated by members of our group that the SR-A1 gene is constitutively expressed in most of the human tissues, while its transcription is increased in breast carcinoma cell lines. Moreover, the SR-A1 gene is overexpressed in a set of ovarian tumors, suggesting that it may be involved in the pathogenesis and/or progression of ovarian cancer. Therefore, in the present study we examined the expression of the SR-A1 gene in colon cancer tissues by RT-PCR and found that it is overexpressed as compared to normal mucosa (p=0.01). The SR-A1 gene was expressed more frequently in well-differentiated tumors than those with poor differentiation. Survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that SR-A1-positivity is associated with a long survival (p=0.044). However, when entered into a Cox multivariate model adjusted for other clinicopathological features studied, SR-A1 expression status was not found to be of independent prognostic significance. To the best of our knowledge, this is the first study examining the expression of the novel gene SR-A1 in colon cancer progression.