RESUMEN
BACKGROUND: Identification of markers associated with melanoma progression is crucial to identify new prognostic and/or therapeutic targets. MATERIALS AND METHODS: By using DNA microarrays, two human melanoma cell lines, M4Be and Tw12, derived from the same tumor, but with different metastatic potential, were profiled. Western blot of cell lines, immunohistochemistry on melanoma biopsies and in silico analyses validated and extended our results. RESULTS: Thirty-six clones were differentially-expressed between the two cell lines, representing 33 named genes and 2 expressed sequence tags. The most up-regulated gene in the strongly metastatic clone Tw12 was CD10. Protein analysis with anti-CD1O antibody confirmed this finding in cell lines and clinical samples with expression being more frequent in metastatic compared to primary tumors. Many up-regulated genes were involved in angiogenesis, invasion, growth and apoptosis. Down-regulated genes included tumor suppressor genes and those were involved in differentiation. CONCLUSION: We identified several genes the expression of which is associated with metastatic progression in human melanoma cells. Although further analyses are warranted to clarify their exact role in tumor progression, they might lead to new prognostic markers and/or molecular therapeutic targets in metastatic melanoma.
Asunto(s)
Biomarcadores de Tumor/genética , Melanoma/genética , Biomarcadores de Tumor/biosíntesis , Línea Celular Tumoral , Perfilación de la Expresión Génica , Humanos , Melanoma/metabolismo , Melanoma/patología , Neprilisina/biosíntesis , Neprilisina/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , PronósticoRESUMEN
BACKGROUND: Androgen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men. METHODS: We used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy. RESULTS: FGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages. CONCLUSION: Our results suggest that each of these four genes may play a role, or at least reflect a stage of prostate carcinoma growth/development/progression.
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Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Biomarcadores de Tumor/aislamiento & purificación , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Proteínas WT1/metabolismo , Animales , Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Proteínas Fetales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Antígeno MART-1 , Masculino , Ratones , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Estadificación de Neoplasias/métodos , Proteínas Nucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Conventional cytogenetic analysis currently stratifies acute myelogenous leukaemia (AML) into prognostically relevant groups. However, approximately 50% of adult AMLs have normal cytogenetics (NC-AMLs), and represent a heterogeneous and poorly understood group. We analysed gene expression in 55 AML samples including 53 cases from adult patients with NC-AML (n = 36), trisomy 8, t(15;17), t(8;21), t(11;19), 7q deletion, and two cell lines using 9000-gene DNA microarrays. Global hierarchical clustering showed that NC-AMLs are a heterogeneous group. Supervised analysis distinguished two subgroups of NC-AML: one subgroup constituted a homogeneous NC cluster ('pure NC-AML'), and the other NC-AMLs were close to the AML cases with translocations ('translocation like'). Gene expression signatures were also derived for patients with trisomy 8, as well as FLT3 and MLL gene duplications. Importantly, samples from 24 NC-AML patients who could be evaluated for clinical outcome were analysed. In all, 43 genes that discriminated two classes of patients with significantly different prognosis were identified. The poor prognosis class contained a majority of 'pure NC-AMLs', whereas the 'translocation-like' AMLs were in the good prognosis class. Discriminator genes included genes involved in drug resistance (TOP2B), protein transport (MTX2, SLC35A2), and cell signalling (MAPK1, PRKAB2). Our results demonstrate the transcriptional heterogeneity of NC-AMLs, and suggest the existence of 'translocation-like' NC-AMLs and of a gene expression signature that may predict response to chemotherapy.