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)

A cell line, designated OSrb/N-M, was established from the second primary osteosarcoma that developed in a 17-year-old Japanese female patient who had suffered from bilateral retinoblastoma at infancy. The OSrb/N-M cells grew as an adherent monolayer and retained some osteogenic biochemical phenotypes. In cytogenetic analyses, this cell line revealed many structural and numerical abnormalities, however, the bands q14 of both chromosomes 13 appeared to be normal, whereas the constitutional cells displayed normal female karyotypes. Immunoblot studies using monoclonal antibodies specific to RB protein demonstrated that the tumor cells did not express RB protein, suggesting that the OSrb/N-M cells might suffer from a loss-of-function mutation at this gene locus. Thus, this cell line is useful to study the molecular mechanism for the tumorigenesis of osteosarcoma with regard to an association with retinoblastoma.
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PMID:Establishment and characterization of a second primary osteosarcoma cell line (OSrb/N-M) from a patient cured of bilateral retinoblastoma. 1007 19

The region q13-15 of chromosome 12 contains SAS, CDK4, and MDM2 genes that are rearranged or amplified in a variety of human sarcomas. This study evaluated SAS gene amplification, and MDM2 and CDK4 protein expression in 20 tumor samples of central low-grade osteosarcoma (16 primary, 3 recurrences, 1 lung metastasis). SAS amplification was analyzed by quantitative polymerase chain reaction (PCR), while from the same paraffin-embedded samples, MDM2 and CDK4 protein expression was evaluated by immunohistochemistry. MDM2 and CDK4 proteins were found strongly expressed in 35% and 65%, respectively, of the samples. SAS was found amplified in 15% of the samples. These findings indicate that these genes may be involved in tumorigenesis and progression of low-grade osteosarcoma.
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PMID:Analysis of SAS gene and CDK4 and MDM2 proteins in low-grade osteosarcoma. 1010 94

The structure of the 17p amplicon from 9 human sarcoma specimens evaluated by comparative genomic hybridization (CGH) has been studied by analyzing 28 microsatellite markers by PCR. Eleven sarcoma specimens showing no DNA copy number increases at 17p by CGH were analyzed as control samples. Five specimens were analyzed by Southern blotting using probes that have previously shown amplification at the 17p12 region in astrocytoma and high-grade osteosarcoma samples. Microsatellite marker analyses revealed that all samples but 1 showing copy number increases at 17p by CGH displayed allelic imbalance that confirmed the CGH findings. Seven of these 9 cases displayed gain in copy number by microsatellite marker analysis. Four cases displaying gain in copy number were associated with loss of heterozygosity at other loci. Southern blot analysis showed amplification in 3 cases, all of them had shown copy number increases by CGH and microsatellite marker analysis, except one case, which was not included in the microsatellite marker analysis. Our results reveal the complexity of the 17p amplicon in sarcomas, suggesting that multiple target genes are involved in tumorigenesis.
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PMID:Characterization of the 17p amplicon in human sarcomas: microsatellite marker analysis. 1039 48

The cyclin-dependent kinase (cdk) inhibitors are key regulators of cell cycle progression. p27 and p21 are members of the Cip/Kip family of cdk inhibitors and regulate cell growth by inactivating cell cycle stage-specific CDK-cyclin complexes. Because down-regulation of osteoprogenitor proliferation is a critical step for osteoblast differentiation, we investigated expression of p27 and p21 during development of the osteoblast phenotype in rat calvarial osteoblasts and in proliferating and growth-inhibited osteosarcoma ROS 17/2.8 cells. Expression of these proteins indicates that p21, which predominates in the growth period, is related to proliferation control. p27 levels are maximal postproliferatively, suggesting a role in the transition from cell proliferation to osteoblast differentiation. We directly examined the role of p27 during differentiation of osteoprogenitor cells derived from the bone marrow (BM) of p27-/- mice. BM cells from p27 null mice exhibited increased proliferative activity compared with BM cells from wild-type mice and formed an increased number and larger size of osteoblastic colonies, which further differentiated to the mineralization stage. Although p27-/- adherent marrow cells proliferate faster, they retain competency for differentiation, which may result, in part, from observed higher p21 levels compared with wild type. Histological studies of p27-/- bones also showed an increased cellularity in the marrow cavity compared with the p27+/+. The increased proliferation in bone does not lead to tumorigenesis, in contrast to observed adenomas in the null mice. Taken together, these findings indicate that p27 plays a key role in regulating osteoblast differentiation by controlling proliferation-related events in bone cells.
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PMID:The cell cycle regulator p27kip1 contributes to growth and differentiation of osteoblasts. 1044 85

We recently obtained 3 cloned cell lines demonstrating the p53 mutation from a lung metastatic nodule of a rat transplantable osteosarcoma. In this study, we applied wild-type p53 gene transfer to the rat osteosarcoma cells by lipofection to investigate the effects on cell growth, expression of genes such as waf1/p21, bcl-2, and bax, and nucleosomal DNA fragmentation due to apoptosis. Reconstitution of the p53 gene inhibits cellular growth, and this growth-suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in this tumor type. This rat osteosarcoma model is similar in biologic behavior to human cases and thus is very suitable for further investigation of tumorigenesis and gene therapy for osteosarcoma.
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PMID:Possible involvement of bcl-2 suppression in wild-type p53 gene-dependent cell growth repression in rat osteosarcoma cells. 1093 45

Mature adult mice of the C57BL/6-TgN(Amy1TAg)501Knw transgenic mouse lineage, 501, containing a liver alpha-amylase promoted-SV40 Tag hybrid gene, routinely develop SV40 Tag-induced metastatic osteosarcomas. This form of alpha-amylase was known to be expressed in the liver, salivary glands, pancreas, and fat. Cells in the normal rib adjacent to the periosteum also express alpha-amylase suggesting that transgene expression is correctly targeted to generate osteosarcomas. 501 mice express SV40 Tag in the salivary glands but do not develop abnormalities in these organs by the time of their death from SV40-induced osteosarcomas. Mice of the C57BL/6 strain make a strong and effective anti-tumor immune response to SV40 Tag immunization. However, immunization of 501 mice with SV40 Tag early in life does not alter or prevent SV40 Tag-induced osteosarcomagenesis. 501 mice mount a significantly less effective cytotoxic T-lymphocyte response following SV40 Tag immunization while 501 osteosarcoma-derived cells are fully susceptible to SV40 Tag-specific T-cell lysis. This suggests that partial tolerance, not loss of antigen presentation by tumor cells, characterizes this mouse model of endogenous bone tumor development. To determine whether the immune recognition of endogenous SV40 Tag could influence tumorigenesis, the metastatic potential and time of death from tumor was investigated in CD4-null mutant 501 mice and beta-2 microglobulin-null mutant 501 mice. The size and number of metastases in these strains and longevity of these strains varied. We suggest that components of both the innate and adaptive immune response control tumor appearance and progression.
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PMID:Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. 1095 95

Osteosarcoma (OS) is a malignant neoplastic disease of the bone, of mesenchymal origin and with considerable morphologic heterogeneity, consisting of malignant stoma with evidence of malignant osteoid, bone and/or cartilage production. The mammalian homeobox (HOX) represents a highly conserved DNA motif of 183 base pairs, encoding the 61 amino acid DNA-binding homeodomain, through which the HOX gene products regulate the transcription of other genes involved in onto- and histogenesis. Re-expression of HOX proteins has been identified in a wide variety of neoplastically transformed cell types and it seems that the HOX genes represent yet another family of oncofetal antigens involved in both normal development and oncogenesis, as well as tumor tissue progression. During this study, the expression pattern of three HOX gene products (HOX-C6, -B3, and -B4) was examined immunocytochemically in human osteosarcoma (OS) tissues. In all observed (16/16) OS cases, HOX-C6 was present in over 90% of the neoplastically transformed cells (+4), demonstrating a high to medium grade (A to B) staining intensity. Similar results were obtained in OS cells for the other two observed proteins (HOX-B3 and -B4; over 90% or +4 and a high to medium grade staining intensity or A and B). The significance of the expression of class I HOX proteins in the pathobiology, diagnosis and prognostication of human OS should be established by further investigations.
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PMID:Homeobox B3, B4, and C6 gene product expression in osteosarcomas as detected by immunocytochemistry. 1095 49

The pituitary tumor transforming gene, PTTG, is abundantly expressed in several neoplasms. We recently showed that PTTG overexpression is associated with apoptosis and therefore have now studied the role of p53 in this process. In MCF-7 breast cancer cells that express wild type p53, PTTG overexpression caused apoptosis. p53 was translocated to the nuclei in cells expressing PTTG. Overexpression of p53, along with PTTG, augmented apoptosis, whereas expression of the human papillomavirus E6 protein inhibited PTTG-induced apoptosis. In MG-63 osteosarcoma cells that are deficient in p53, PTTG caused cell cycle arrest and subsequent apoptosis that was inhibited by caspase inhibitors. A proteasome inhibitor augmented PTTG expression in stable PTTG transfectants, suggesting that down-regulated PTTG expression is required for cell survival. Finally, MG-63 cells expressing PTTG showed signs of aneuploidy including the presence of micronuclei and multiple nuclei. These results indicate that PTTG overexpression causes p53-dependent and p53-independent apoptosis. In the absence of p53, PTTG causes aneuploidy. These results may provide a mechanism for PTTG-induced tumorigenesis whereby PTTG mediates aneuploidy and subsequent cell transformation.
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PMID:Pituitary tumor transforming gene causes aneuploidy and p53-dependent and p53-independent apoptosis. 1101 29

Inactivation of wild-type p53 tumor suppressor function is the primary mechanism of tumor initiation in Li-Fraumeni syndrome (LFS) individuals with germline p53 mutations. Tumors derived from LFS patients frequently retain the normal p53 allele, suggesting that alternative mechanisms in addition to gene deletion must be involved in inactivating wild-type p53 protein. DNA tumor viruses, such as SV40, target p53 for inactivation through the action of viral oncoproteins. We studied the probands from two unrelated LFS families, each of whom presented with multiple malignant neoplasms. Patient 1 developed an embryonal rhabdomyosarcoma (RMS) and a choroid plexus carcinoma (CPC), while patient 2 developed a CPC and subsequently presented with both an osteosarcoma (OS) and renal cell carcinoma (RCC). We utilized DNA sequence analysis and immunohistochemistry to determine p53 gene status in the germline and tumors, as well as evidence for SV40 T-antigen oncoprotein expression. Each patient harbored a heterozygous germline p53 mutation at codons 175 and 273, respectively. In patient 1, the normal p53 gene was lost while the mutant p53 allele was reduced to homozygosity in the RMS. Both normal and mutant genes were maintained in the CPC. In patient 2, normal and mutant p53 alleles were retained in both the CPC and RCC. Both specific PCR and immunostaining detected SV40 T-antigen in both CPCs and the RCC. In addition to chromosomal alterations, epigenetic mechanisms may disrupt p53 function during tumorigenesis. In two LFS patients, we found SV40 DNA sequences and viral T-antigen expression that could account for inactivation of the normal p53 protein. Inactivation of p53 or other tumor suppressors by viral proteins may contribute to tumor formation in specific tissues of genetically susceptible individuals.
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PMID:Tissue-specific expression of SV40 in tumors associated with the Li-Fraumeni syndrome. 1149 39

p53, a tumor suppressor gene, is a target of genetic alternations in many human and animal cancers. Compared to normal tissues, cancer tissues overexpress mutant p53 protein thus allowing their detection by a number of immunochemical procedures. To what extent the expression of mutant p53 correlates with dog mammary tumorigenesis has not been fully studied. In the present study, 20 spontaneously arising canine mammary tumors were examined for overexpression of mutant p53. Two different monoclonal antibodies, BP53-12 and PAb122, which recognize different epitopes of the p53 product, were used. The canine tumors in the present study exhibited five different histological types: i) osteosarcoma (n=7); ii) carcinosarcoma (n=4); iii) solid carcinoma (n=5); iv) complex carcinoma (n=3); and v) tubulopapillar carcinoma (n=1). The positive ratios against BP53-12 and PAb122 antibodies were 50% (10/20) and 60% (12/20) respectively. Among these positive samples, 35% (7/20) reacted to both antibodies. Finally, 15 out of 20 tumors showed positivity against one of the monoclonal antibodies. Mostly, as in human mammary tumor cells, BP53-12 staining was observed in the nuclei of tumor cells. PAb122 staining, however, was confined to cytoplasm of osteosarcoma or carcinosarcoma cells. To confirm the location of the staining, immunoelectron microscopy was done. The results showed that the cytoplasm of cartilage cells in the sarcomas had positive staining. These results indicate that anti-p53 antibodies BP53-12 and PAb122, generated against human p53 are cross reacting with the same molecule in canine cells and that the role of p53 in tumorigenesis is not only confined to tumors in human. Our finding suggests that a combination of p53 monoclonal antibodies should be used to screen, not only canine mammary tumors but also human mammary tumors, to obtain a better tumor prognosis.
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PMID:Overexpression of the p53 gene product in canine mammary tumors. 1160 35


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