Apoptotic genes as potential markers of metastatic phenotype in human osteosarcoma cell lines

Abstract

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 (GADD45α, VCP, DHX9, survivin, α-catulin, ARPC1B) related to growth arrest and apoptosis. Most of these genes are functionally related with the nuclear factor (NF)-κB cell survival pathway that appeared to be inhibited in the less malignant osteosarcoma cells. Hence, we propose the inhibition of the NF-κB pathway as a rational strategy for effective management of human osteosarcoma.

Overexpression of mitogen-activated protein kinase kinase 4 and nuclear factor-κB in laryngeal squamous cell carcinoma: A potential indicator for poor prognosis

“…There is now considerable evidence that sustained or constitutive activation of NF-κB is prevalent in cell lines and tumor tissue specimens and contributes to malignant progression in most of the major forms of human cancer (18)(19)(20)(21)(22). Our results showed obvious overexpression of NF-κB in human LSCC tissues as compared with the adjacent normal tissues.…”

VCP Mutations Causing Frontotemporal Lobar Degeneration Disrupt Localization of TDP-43 and Induce Cell Death

“…VCP has been shown to be phosphorylated by AKT and also has a role in ubiquitination of IB␣ activating the NF-B cell survival pathway (21,35,53). Modulation of VCP expression has been implicated in cancer and apoptotic pathways (56,72). Proteasome malfunction has been shown to activate the caspase cascade and, eventually, apoptotic cell death (69).…”

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

“…32 In human osteosarcoma, genes relating to apoptosis exist in the downstream of NF-kB signaling. 33 Asai et al 14 showed in an in vitro study that transfecting valosin-containing protein (VCP; an inactivator of inhibitor-kB) into osteosarcoma cells significantly decreased the rate of apoptosis compared with non-treated osteosarcoma cells. In our study, the DNA-binding activity of NF-kB by LM8 cells was markedly inhibited by transfection of NF-kB decoy ODN.…”