Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have shown earlier that 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3] induces cell growth suppression and cell differentiation of a human megakaryoblastic leukemia cell line, HIMeg. However, the molecular mechanism of 1,25(OH)2 D3 action is still unknown. Prompted by this, we have searched here for the presence of 1,25(OH)2 D3 receptor (VDR) expression in HIMeg cells by reverse transcription-polymerase chain reaction (RT-PCR). The amplified product showed an identical size to the product amplified from the control human VDR cDNA and hybridized specifically with the digoxigenin-labeled human VDR cDNA fragment. As expected, VDR mRNA is also expressed in HOS-8603, a human osteosarcoma cell line. These results represent the first reported evidence that VDR mRNA is expressed in megakaryoblastic cells. In addition, the regulation of VDR mRNA expression in HIMeg cells was studied by quantitative RT-PCR. It was found that [correction of the] VDR mRNA expression in HIMeg cells could be down-regulated rapidly by 1,25(OH)2 D3 (10 nM) in a time-dependent manner, reaching a maximal reduction to about 15% of control. However, VDR mRNA expression in HOS-8603 cells was not regulated by 1,25(OH)2 D3 at any time-point tested. Treatment of HIMeg cells with forskolin (1 microM), an activator of adenylate cyclase, caused an increase in VDR mRNA levels. Similarly, VDR mRNA expression in HOS-8603 cells was also up-regulated by forskolin. Consistent with the functionality of the VDR in other target cells, we found that the up-regulation of VDR expression in HIMeg cells by forskolin was accompanied by an increased responsiveness of HIMeg cells to 1,25(OH)2 D3 even though forskolin alone had no effects. Exposure to 1,25(OH)2 D3 in combination with forskolin resulted in a much more significant inhibition of cell proliferation than to 1,25(OH)2 D3 alone. Similarly, forskolin could also augment the differentiation induced by 1,25(OH)2 D3 reflected by a more evident morphological change and a higher percentage of development of cells with multilobular nuclei. These alterations were accompanied by a loss of clonogenic capacity and a decrease in the number of cells in the S phase. These data establish that HIMeg cells express functional VDR, which served to mediate actions of its ligand on the proliferation and differentiation of these cells.
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PMID:Demonstration of vitamin D receptor expression in a human megakaryoblastic leukemia cell line: regulation of vitamin D receptor mRNA expression and responsiveness by forskolin. 863 62

Previously, it has been found that glucocorticoid receptor (GR) binding activity decreased rapidly during heat shock response in HOS-8603, a human osteosarcoma cell line. In this study, The relationship between the induction of heat shock proteins (HSPs) and the decrease in GR was further studied in the same cell line. It was found that even though quercetin could specifically inhibit the expression of hsp90 alpha and hsp70 mRNA, it could not prevent GR from the decrease in response to the heat shock treatment. This represents the first reported evidence that the induction of HSPs and the decrease in GR during heat shock response were 2 independent biological events. The results of the present study further showed that although the heat shock treatment alone had no effects on alkaline phosphatase (AKP) activity, it could completely block the induction of AKP activity in HOS-8603 cells by dexamethasone (Dex), a synthetic glucocorticoid. These results demonstrate that the heat shock-induced alteration in GR was accompanied by a decrease in GR functional activity. Furthermore, when the induction of HSPs was inhibited by the treatment of cells with quercetin, the stimulatory effects of Dex on AKP activity could still be inhibited completely by the heat shock treatment. The results of this part, on the basis of GR functional activity, further demonstrate that quercetin could not inhibit the heat shock-induced decrease in GR even though it could inhibit the induction of HSPs. To clarify further the effects of quercetin alone on GR binding activity in HOS-8603 cells, the regulation of GR by quercetin was also studied. It was found for the first time that quercetin could down-regulate GR in a time-dependent manner significantly, and that the down-regulation of GR by quercetin in HOS-8603 cells paralelled with a decrease in glucocorticoid-mediated functional responses, suggesting that the down-regulation of GR by quercetin is of biological significance.
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PMID:Relationship between the induction of heat shock proteins and the decrease in glucocorticoid receptor during heat shock response in human osteosarcoma cells. 874 75

NK cells are CD16, CD56 positive lymphocytes that spontaneously lyse tumor or virus infected cells. In this study we investigated whether IL-2 and/or IL-12 stimulated NK cells increased their lytic efficiency against HOS osteosarcoma cell line. Our results demonstrate that both 18 hour and 5 day incubation times enhanced the lytic activity of human PBL against HOS and K562 target cells and that IL-12 appears to be more efficient than IL-2 in augmenting NK cytotoxicity.
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PMID:Lytic activity of IL-2 and IL-12 stimulated NK cells against HOS osteosarcoma cell line. 886 11

Our previous experiments have indicated that the antitumor effects of a polyamine biosynthetic inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), on human osteosarcoma cell lines such as MG-63, G-292 and HOS cells are obtained by its action depleting the cellular polyamine contents. In the present study, the effects of polyamine depletion by MGBCP on the cell cycle progression in these osteosarcoma cell lines were investigated by flow cytofluormetric analysis. MGBCP arrested the tumor cells at the G1 phase by preventing the G/S phase transition. Mitotic indexes (MIs) in these MGBCP-inhibited tumor cells were also decreased. These findings suggest that MGBCP suppresses the cell cycle progression in osteosarcoma MG-63, G-292 and HOS cells by inhibiting intracellular polyamine biosynthesis.
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PMID:Effects of methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP) on cell cycle progression in three human osteosarcoma cell lines. 891 52

We investigated whether stromal cells obtained from human tonsils could interact and modulate the proliferation of the osteosarcoma cell in order to determine why lymph node metastases usually have a low incidence and remain occult using routine examinations. The effects of the supernatant of resting or activated stromal cells were analysed on osteoblastic cell proliferation of three different cell lines (HOS, U2, OS, MG-63). Only the proliferation of MG-63 was significantly inhibited. The direct adhesion of stromal cells to the osteosarcoma cell lines caused a greater inhibition of the proliferation of all three lines tested.
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PMID:Effect of stromal cells from human lymph nodes on the growth of osteosarcoma cell lines. 896 96

Alkaline phosphatase (ALP) plays an important role in bone mineralization; high levels in differentiated osteoblasts allows their identification easily in vitro. It is generally assumed that the activity of ALP in osteosarcoma-derived cell lines commonly used in studies of bone cell biology is exclusively due to the bone/liver/kidney (BLK) isoenzyme. However, we noted that two human osteosarcoma cell lines, U-2 OS and U-393 OS, predominantly expressed a truncated 1.8 kb mRNA for BLK-ALP. This observation stimulated further investigation upon the ability of ALP to form functional protein. We found that, unlike the BLK-ALP of the Saos-2 osteosarcoma cell line, the activity of U-2 OS ALP was thermostable, unaffected by L-homoarginine and levamisole, but inhibited by L-phenylalanine; these properties are characteristic of the placental and/or placental-like (PL-/PL-like ALP) isoenzymes which are 98% homologous at the amino acid level. In the U-393 OS cell line, which expresses the normal-sized 2.5 kb mRNA in substantially higher levels than that produced by U-2 OS cells, the ALP activity had kinetic properties very similar to that produced by the Saos-2 line for all criteria tested. The HOS osteosarcoma cell line (also known as TE-85), which express the normal-sized 2.5 kb BLK-ALP mRNA only, exhibited ALP activity with kinetic properties of both the BLK and PL-/PL-like isoenzymes. The three test lines, U-2 OS, U-393 OS and HOS, produced PL-/PL-like ALP mRNA and protein constitutively, and levels of these increased in cells treated with 1 microM dexamethasone. However, dexamethasone treatment of cells did not alter the types of ALP isoenzyme expressed. Thus our results show that, like Saos-2 cells, U-393 OS cells produce active BLK-ALP exclusively, whereas U-2 OS cells produce PL-/PL-like ALP only, and the HOS cell line produces both. Our findings have important implications for phenotypic characterization of various human osteosarcoma cell lines, and suggest that the production of PL-/PL-like ALP may be a more common occurrence in osteosarcomas than was originally thought.
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PMID:Constitutive expression of non-bone/liver/kidney alkaline phosphatase in human osteosarcoma cell lines. 899 82

Bone morphogenetic proteins (BMPs) are a group of peptide growth factors closely related to transforming growth factors-beta. The BMPs are suggested to play an essential role in bone development and they are strong candidate molecules to be used clinically to improve fracture healing. BMPs are also involved in the differentiation of several other tissues during embryogenesis. Here, we show that human recombinant BMP-2 regulates cell-matrix interactions by modifying the expression of integrin-type receptors. The synthesis of alpha3 integrin was down-regulated by BMP-2 in two osteogenic sarcoma-derived cell lines, Saos-2 and HOS, and also in human fetal chondrocytes. BMP-2 had no effect on the expression of alpha1, alpha2, alpha5, alpha6, and alphaV integrins. BMP-2 reduced the expression of alpha3 integrin subunit at mRNA level. Laminin-5 was shown to be the ligand for alpha3beta1 integrin on Saos cells and BMP-2 decreased the ability of Saos cells to attach to it. These results suggest that BMP-2 has a specific effect on the alpha3beta1 integrin-mediated cell adhesion to laminin-5. Given the fact that BMP-2 is expressed in osteosarcomas, in addition to in bone, this mechanism is putatively important especially in bone development and tumors. We also studied the effect of BMP-2 on a human keratinocyte cell line, HaCaT. In HaCaT cells, the expression of alpha2 integrin was strongly down-regulated by BMP-2, whereas its effect on the expression of alpha3 integrin was smaller. We suggest that the effects of BMP-2 may be partially mediated by specifically altered cell adhesion.
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PMID:Bone morphogenetic protein-2 is a regulator of cell adhesion. 902 97

In order to investigate the subnuclear interactions of the WT1 gene product, nuclear fractionation analyses were performed with human osteosarcoma HOS and myelogenous leukemia K562 cells. The WT1 protein was tightly associated with the nucleus and was resistant to high-salt or detergent extraction and DNase I digestion. Both the expression level and stability of WT1 and its resistance to high salt and DNase I treatments remained constant during the cell cycle. In addition, human WT1 ectopically expressed in mouse NIH3T3 cells was also resistant to these treatments. These results suggest that WT1 functions in tight association with the nuclear matrix.
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PMID:The Wilms tumor protein is persistently associated with the nuclear matrix throughout the cell cycle. 920 4

To investigate the functional differences between estrogen receptor (ER) alpha and beta subtypes, we studied the expression and the transcription stimulating activities of these receptors. RT-PCR has demonstrated that ER alpha is expressed at a high level in MCF-7 cells derived from human breast cancer. Both ER alpha and ER beta were expressed at a lower level in HOS-TE85 and Saos2 cells derived from human osteosarcoma. Chloramphenicol acetyltransferase reporter assay detected the transcriptional activation by the endogenous receptor only in MCF-7 cells. Agonistic effect of tamoxifen was observed as strong as that of 17beta-estradiol on ERE activation in MCF-7 cells at the concentration of 10(-7) M when ERE-containing reporter is constructed with beta-globin promoter. The effect of tamoxifen was not apparent when the reporter was constructed with thymidine kinase promoter, suggesting that the differential gene activation between tamoxifen and estrogen may take place depending upon ERE-promoter context. Agonistic activity of tamoxifen was also detected in COS-7 and Saos-2 cells, but not in HEC-1 cells derived from human endometrial carcinoma via exogenously expressed ER. Interestingly, this effect was ER alpha specific. Thus, we demonstrate that agonistic effect of tamoxifen depends on the cell type, ERE-promoter context, and ER subtype. These parameters would explain at least a part of the tissue specific effects of antiestrogens in vivo.
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PMID:Agonistic effect of tamoxifen is dependent on cell type, ERE-promoter context, and estrogen receptor subtype: functional difference between estrogen receptors alpha and beta. 922 41

The CD95/APO-1 Fas receptor/ligand system plays a crucial role in growth control by mediating apoptosis in lymphoid and non-lymphoid cells. To investigate the role of CD95-mediated apoptosis in osteosarcoma, we studied 3 human osteosarcoma cell lines (HOS/TE 85, MG 63 and Saos-2) and osteoblasts derived from bone biopsies. In contrast to osteoblast-like cells, all cell lines were resistant to anti-APO-1-induced apoptosis despite constitutive CD95 expression at intermediate levels. Blocking of macromolecular synthesis by cycloheximide or actinomycin D or modulation of CD95 expression by cytokines (TNF-alpha and/or gamma-interferon) restored sensitivity to anti-APO-1-induced cell death. PCR analysis of the CD95 transcripts revealed the production of a truncated splice variant that codes for a soluble form of the CD95 receptor. Synthesis and secretion of soluble CD95 protein into the culture supernatant was demonstrated by Western blot analysis. Treatment with sensitizing cytokines led to up-regulation of full-length CD95 transcripts and the encoded membrane-bound CD95 protein but not the truncated mRNA splice variant and the corresponding soluble receptor, as shown by PCR and Western blot analysis. The biological activity of soluble CD95 secreted by osteosarcoma cells was demonstrated by the ability of osteosarcoma supernatants to protect the sensitive T-cell line Jurkat from anti-APO-1-mediated apoptosis. Our results suggest that the production of soluble CD95 by osteosarcoma cell lines that may block physiological death signals and the production of membrane-bound CD95 are differently regulated by cytokines via modulation of RNA splicing.
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PMID:Modulation of resistance to anti-APO-1-induced apoptosis in osteosarcoma cells by cytokines. 924 1


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