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)

Amplification and rearrangement of cellular proto-oncogenes are two of the several possible genetic alterations implicated in carcinogenesis and tumor progression. Although morphologically similar tumors may be heterogeneous at the level of the genome, some tumor types have shown relatively frequent and consistent abnormalities of specific oncogenes. In order to determine the frequency of oncogene amplification and rearrangement in several types of human sarcomas and to determine if histologically similar tumors have common genetic alterations, we analyzed 26 primary sarcomas by Southern hybridization. The oncogene probes utilized were N- and H-ras, sis, EGF-R (erb-B-1), neu (erb-B-2), fos, N- and c-myc, mos, and yes. The tumors studied included: five rhabdomyosarcomas (one alveolar, four embryonal), six malignant fibrous histiocytomas, six leiomyosarcomas, four liposarcomas, two Ewing's sarcomas, one osteosarcoma, and two fibrosarcomas. Oncogene abnormalities were identified in three tumors. One rhabdomyosarcoma showed 12-fold amplification and concurrent rearrangement of sis. This particular tumor also revealed rearrangement of H-ras and 15-fold amplification of c-myc. A second rhabdomyosarcoma revealed rearrangement of neu. A liposarcoma had a sis rearrangement. These findings suggest that many sarcomas show no common structural oncogene abnormalities. The presence of differing oncogene alterations within the rhabdomyosarcoma group indicates genetic heterogeneity among histologically similar sarcomas. The finding of a sis rearrangement in both a liposarcoma and a rhabdomyosarcoma, however, may suggest common oncogenesis among different tumor types.
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PMID:Genomic alterations in sarcomas: a histologic correlative study with use of oncogene panels. 149 46

We examined structure and expression of the p53 and Rb genes in a C3HOS transplantable mouse model of osteosarcoma. The results were compared to analogous studies conducted with five human osteosarcoma cell lines. The p53 gene was found rearranged in the mouse tumour. The rearrangement mapped to the first intron region of the p53 gene and as a result, no p53 expression could be detected in C3HOS tumours. Using p53 genomic probes, we have detected the same rearrangement in the original radiation-induced tumour and the various clones that were isolated from it. Deletion and rearrangement of the p53 gene were also found in three out of five of the human osteosarcoma cell lines (MG-63, G-292, Saos-2). No p53 expression could be detected in these three cell lines. In the affected human osteosarcoma cell lines, the rearrangement involved the first intron region. In addition, the mouse tumor was analysed for structural and expression changes in the Rb and the c-myc genes. Normal expression of both genes were detected in the murine tumour. Only one (Saos-2) human osteosarcoma cell line exhibited gross structural alteration in the retinoblastoma gene. The results suggest that the inactivation of p53 may be an important step in the development of osteosarcomas, and that a rearrangement affecting the first intron is common in osteosarcomas.
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PMID:Inactivation of p53 gene in human and murine osteosarcoma cells. 173 19

The heterologous regulation of hormone receptors is well described in the hormone receptor literature. We were interested in determining whether human 1,25-dihydroxyvitamin D-3 receptor (hVDR) and glucocorticoid receptor (GR), members of the steroid/thyroid hormone receptor family, are heterologously regulated by other steroids and related hormones. We used human osteosarcoma cells (MG-63) and measured hVDR and GR mRNA levels after androgen, estrogen, glucocorticoid, progesterone, thyroid hormone, vitamin A and vitamin D treatments. Each hormone, except androgen and progesterone, was capable of increasing hVDR mRNA levels like the natural ligand in human osteosarcoma cells. On the other hand, GR gene expression was not affected by these hormones. To study whether the cells responded to the 1,25(OH)2D3-treatment with changes in differentiation and proliferation, we also studied c-myc and c-fos gene expression. Both genes were only regulated by 1,25(OH)2D3. 1,25(OH)2D3 slightly increased the accumulation of c-fos mRNA within 4-12 h from the hormone addition, while the increase in c-myc mRNA appeared at 24 h.
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PMID:Homologous and heterologous regulation of 1,25-dihydroxyvitamin D-3 receptor mRNA levels in human osteosarcoma cells. 184 64

Previous studies have shown that increased expression of oncogenes from the myc-family can down-regulate the level of MHC class I antigens in tumor cells. This has suggested a mechanism by which amplification/overexpression of myc-genes may contribute to the malignancy development of certain tumors. Earlier published data from the murine SEWA tumor, a polyomavirus-induced osteosarcoma, have correlated the degree of tumorigenicity of different sublines to their level of c-myc amplification. Here I present a quantitative and qualitative analysis of MHC class I antigens from five sublines of this tumor system. No differences could be found, between sublines with different degrees of tumorigenicity, regarding MHC class I antigen expression. Thus, in the SEWA tumor, the enhancement of the tumorigenicity caused by c-myc amplification is not mediated through down-regulation of MHC class I antigens.
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PMID:Down-regulation of MHC class I antigens is not a general mechanism for the increased tumorigenicity caused by c-myc amplification. 215 10

Canine and human osteosarcoma are very similar clinically, radiologically and pathologically. DNA extracted from canine osteosarcomas (n = 9) and normal canine control tissues (n = 17) was examined for amplification of the c-sis, c-myc, N-myc and c-H-ras protooncogenes. Statistically significant amplification of the c-sis and c-myc protooncogenes was evident in the tumor tissues as compared to the normal control tissues (P less than 0.05). DNA and total cellular RNA from cultured canine and human osteosarcoma and fibroblast cell lines were examined for amplification or enhanced expression of c-sis and c-myc. Very low levels of c-myc and c-sis DNA amplification were noted in canine osteosarcoma cells as compared to canine fibroblasts. Immunostaining of sections of human and canine osteosarcoma for the sis gene product, PDGF B, showed similar levels and patterns of expression in both populations of tumors.
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PMID:Low level amplification of c-sis and c-myc in a spontaneous osteosarcoma model. 220 81

The platelet-derived growth factor (PDGF) modulated growth response of the MG-63 human osteosarcoma cell line, which neither expresses c-sis mRNA nor secretes a PDGF analogue, was characterized. Scatchard analysis demonstrated that the MG-63 cells have 23,000 receptors per cell with a Kd of 5 X 10(-11) M. The receptor became phosphorylated, in a PDGF concentration-dependent manner, when 32P-orthophosphate-labeled cells were treated with PDGF for 3 h at 4 degrees C. The phosphorylated receptor was identified by autoradiography and gel electrophoresis after isolation of the 32P-labeled receptor using a solid-phase monoclonal antibody directed against phosphotyrosine. Binding of the receptor to the antibody was inhibited by 5 mM phenyl phosphate, further suggesting that PDGF stimulated tyrosine-specific receptor autophosphorylation. In addition, treatment of MG-63 cells with PDGF for 3 h at 37 degrees C induced a 7.5-fold increase in c-myc mRNA accumulation as analyzed on Northern gels. However, MG-63 cells grew equally well in either serum-(which contains PDGF) or plasma-(which does not) supplemented medium. Furthermore, PDGF did not stimulate DNA synthesis in growth arrested MG-63 cells, nor did it potentiate DNA synthesis modulated by somatomedin C. Thus MG-63 cells are a naturally occurring cell variant in which PDGF stimulates c-myc expression but does not modulate mitogenesis.
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PMID:PDGF induces c-myc mRNA expression in MG-63 human osteosarcoma cells but does not stimulate cell replication. 243 22

Platelet-derived growth factor (PDGF) is generally considered to stimulate phosphoinositide turnover resulting in activation of protein kinase C and increased cytoplasmic [Ca2+]. We have examined the role of these secondary effects in regulation of c-myc mRNA accumulation in the MG-63 human osteogenic sarcoma line. Treatment of quiescent cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) to down-regulate protein kinase C inhibited TPA-stimulated c-myc expression but did not affect the PDGF-modulated process. When cytoplasmic [Ca2+] was increased by addition of a Ca2+ ionophore (A23187 or ionomycin), no stimulation of c-myc RNA was seen; furthermore, these agents did not enhance the PDGF-modulated c-myc expression. Addition of EGTA to cultures treated with both PDGF and a Ca2+ ionophore did not inhibit c-myc induction but rather caused a superinduction of c-myc RNA accumulation. Superinduction occurred only if the [EGTA] was greater than [Ca2+] in the medium. This superinduction was distinct from the increased induction caused by inhibition of protein synthesis. Because PDGF-induced c-myc expression is independent of protein kinase C and increased cytoplasmic [Ca2+], the evidence suggests that PDGF modulates c-myc RNA accumulation in MG-63 cells via a novel pathway, seemingly uncoupled from the classic action of increased phosphoinositide metabolism.
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PMID:Platelet-derived growth factor-induced c-myc RNA expression. Analysis of an inducible pathway independent of protein kinase C. 244 30

Human colorectal carcinomas frequently express elevated levels of c-myc mRNA in the absence of a gross genetic change at the c-myc locus. To test the hypothesis that these tumors are defective in a gene function necessary for the regulation of c-myc expression, we fused an osteosarcoma cell line that exhibits normal c-myc regulation with two colon carcinoma cell lines that express deregulated levels of c-myc mRNA. The levels of c-myc transcripts in all of the hybrid clones examined were normal and were induced normally by a mitogenic stimulus. Since rates of c-myc mRNA turnover in the colon carcinoma cells were found to be comparable to those in normal cells, increased message stability cannot account for the increased steady-state levels of transcripts. Our findings suggest that loss of function of a trans-acting regulator is responsible for the deregulation of c-myc expression in a major fraction of colorectal carcinomas. Analysis of restriction fragment length polymorphisms in tumor/normal tissue pairs from patients with primary colorectal lesions indicated that deregulation of c-myc expression in the tumors is correlated with frequent loss of alleles of syntenic markers on chromosome 5q; allele loss on 5q could be detected in 9 of 19 tumors expressing deregulated levels of c-myc mRNA, but not in any of 8 tumors expressing normal levels of c-myc RNA. Chromosome 5q is the region known to contain the gene for familial adenomatous polyposis, an inherited predisposition to colon cancer. These findings, together with the earlier finding that the colonic distribution of tumors exhibiting deregulated c-myc expression is similar to that reported for familial polyposis, provide evidence that loss of function of the familial adenomatous polyposis gene is involved in a subset of colorectal cancers in which c-myc expression is deregulated.
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PMID:Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation. 254 67

Two cell lines were established from a human osteosarcoma transplanted into athymic nude mice after the second (O9N2) and fifth passages (HuO9). Both cell lines expressed 1,25(OH)2D3-responsive alkaline phosphatase activity and produced tumors in the dorsum of nude mice that were histologically similar to the original tumor. However, the morphological and growth characteristics of the two cell lines differed. O9N2 cells were large and polygonal, whereas HuO9 cells showed spindle shapes. HuO9 cells had a higher growth rate and saturation density than O9N2 cells. The c-myc oncogene was amplified 4- to 8-fold in HuO9 cells but not in O9N2 cells. Both cell lines had a homozygous internal deletion, lacking the 7.4-kb HindIII fragment in the Rb gene. The results suggest the importance of the c-myc oncogene in the growth and morphological control of human osteosarcoma cells and of the Rb gene in the pathogenesis of the tumor.
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PMID:Two distinct cell lines derived from a human osteosarcoma. 269 14

In mice, endogenous retroviruses are known to be activated during the course of radiation osteosarcomagenesis. Using the Southern blotting procedure, we have studied the presence of somatically acquired proviruses in genomic DNA isolated from seven primary 90Sr induced osteosarcomas and one osteosarcoma cell line, 0-127a1, of the CF1 mouse strain. Specific hybridization probes demonstrated the presence of newly integrated ecotropic proviruses in four primary tumors. Probably, clonally integrated proviruses were present at distinct locations in different subpopulations of tumor cells, reflecting tumor heterogeneity. Genomic DNA isolated from cultured osteosarcoma cells contained different additional MCF-related proviruses. No proviruses were found integrated in the vicinity of c-myc, but a large domain containing the complete c-myc gene was found amplified in one primary tumor (greater than 22 kbp) and in 0-127a1 cells (greater than 39 kbp). Our data suggest that activated retroviruses are not essential for the development of radiogenic osteosarcomas in CF1 mice, but they might be responsible for the deregulated expression of a growth promoting gene in some bone tumor cells.
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PMID:Provirus integration and myc amplification in 90Sr induced osteosarcomas of CF1 mice. 283 3


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