Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The retinoblastoma (Rb) protein (pRb) has been studied in various crystalline NiS-transformed cell clones derived from the human osteoblast cell line, HOS TE-85. The parental HOS cells were not able to proliferate in soft agar medium, but they acquired this property following treatment with crystalline NiS. The pRb was found only in the hypophosphorylated form in 8 of 9 nickel-transformed clones examined, whereas in the parental cells the pRb appeared in both phosphorylated and unphosphorylated forms. Neither Rb gene expression nor its phosphorylation was affected by acute nickel treatments of HOS cells. The nickel-transformed HOS clones expressed the major regulators of Rb phosphorylation, cyclin E and cdk-2, at levels similar to those of the parental cells. In coimmunoprecipitation assays with cell lysates from the transformed clones that exhibited the hypophosphorylated form of pRb, the Rb protein failed to form a complex with simian virus 40 large T-antigen, indicating a lack of functional activity. When a plasmid containing the normal Rb gene was transfected into these nickel-transformed cells, it restored the Rb phosphorylation pattern observed in parental cells and the cells acquired a normal phenotype (i.e., they were no longer able to grow in soft agar). This suggested that a mutation was induced in nickel-transformed cells that affected the ability of the Rb protein to be phosphorylated and function normally, and this mutation allowed the human nickel-transformed cells to acquire anchorage-independent growth.
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PMID:Nickel-induced transformation of human cells causes loss of the phosphorylation of the retinoblastoma protein. 816 6

Osteosarcomas are genetically complex tumors with abundant structural and numerical alterations. The molecular pathogenesis of the disease is, however, still poorly understood. Aside from various oncogenes and tumor suppressor genes, deregulated microRNAs (miRNAs) are known to influence tumor development and biology. We therefore investigated six well-established osteosarcoma cell lines (HOS58, U2-OS, Saos-2, MNNG/HOS, SJSA-1, and MG-63) for genome-wide miRNA expression (miRBase Version 15.0, http://www.mirbase.org/) and correlated our findings with gene expression. Cultured osteoblasts (hFOB 1.19) and mesenchymal stem cells (L87/4) were used as normal references. Focusing only on miRNAs that were deregulated in the majority of osteosarcoma cell lines, we identified several miRNAs with oncogenic and tumor suppressor properties, including various members of the oncogenic miR-17-92 cluster. In addition, several genes involved in differentiation (RGMB, LRRC17), cell cycle control (CCNE1), and apoptosis (LIMA1, CAMK2N1) were found to be deregulated in osteosarcoma cell lines, most likely due to altered miRNA expression patterns. Our findings indicate a crucial impact of deregulated miRNAs with consecutive changes in gene expression in osteosarcomas, which strongly suggests pathogenetic and potentially therapeutic implications.
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PMID:MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma. 2268 20