title: Apoptotic genes as potential markers of metastatic phenotype in human osteosarcoma cell lines.
abstract: Metastasis is the most frequent cause of death among patients with osteosarcoma. We have previously demonstrated in independent experiments that the forced expression of L/B/K ALP and CD99 in U-2 OS osteosarcoma cell lines markedly reduces the metastatic ability of these cancer cells. This behavior makes these cell lines a useful model to assess the intersection of multiple and independent gene expression signatures concerning the biological problem of dissemination. With the aim to characterize a common transcriptional profile reflecting the essential features of metastatic behavior, we employed cDNA microarrays to compare the gene expression profiles of L/B/K ALP- and CD99-transfected osteosarcoma clones showing low metastatic ability with those of osteosarcoma cell lines showing contrasting behavior. Changes in gene expression were validated by real-time PCR and immunohistochemistry in independent samples. In our study we identified several differentially expressed genes (GADD45alpha, VCP, DHX9, survivin, alpha-catulin, ARPC1B) related to growth arrest and apoptosis. Most of these genes are functionally related with the nuclear factor (NF)-kappaB cell survival pathway that appeared to be inhibited in the less malignant osteosarcoma cells. Hence, we propose the inhibition of the NF-kappaB pathway as a rational strategy for effective management of human osteosarcoma.
authors: Dipartimento di Istologia, Embriologia e Biologia Applicata, Università di Bologna, 40126 Bologna, Italy.
authors: Cinzia
authors: C
authors: Zucchini
authors: Anna
authors: A
authors: Rocchi
authors: Maria Cristina
authors: MC
authors: Manara
authors: Paola
authors: P
authors: De Sanctis
authors: Cristina
authors: C
authors: Capanni
authors: Michele
authors: M
authors: Bianchini
authors: Paolo
authors: P
authors: Carinci
authors: Katia
authors: K
authors: Scotlandi
authors: Luisa
authors: L
authors: Valvassori
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology / Q000556:secondary*; D010641:Phenotype; D015398:Signal Transduction; D000097642:GADD45 Proteins
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019938:Cyclin D1; D016328:NF-kappa B; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins