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)

Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2). RB-1 heterozygosity also predisposes to osteosarcoma, and RB-1 allele losses are seen in sporadic lung, breast, prostate and bladder carcinomas. RB-1 is expressed in most, if not all, tissues and codes for a nuclear phosphoprotein which becomes hypophosphorylated in the G0 growth arrest state and in the G1 phase of the cell cycle. To gain a further insight into the role of RB-1 we and other groups have generated mice carrying an inactivated allele of the homologous gene, Rb-1 (ref. 10), by gene targeting. We report here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency. However, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development. Broadly similar results are reported by the other groups.
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PMID:Requirement for a functional Rb-1 gene in murine development. 140 28

Retinoblastoma tumor formation is initiated by the loss of function of both alleles of the RB-1 gene on chromosome 13. Patients with the hereditary form of retinoblastoma carry a germ line mutation at one of the two homologous gene loci in all cells and have an increased risk for nonocular tumors (mainly osteosarcoma and other mesenchymal tumors) in later life. The authors studied a 38-year-old patient with sinonasal undifferentiated carcinoma (SNUC) who had been treated for bilateral retinoblastoma by enucleation (left eye) and irradiation (right eye), respectively. Using molecular probes for the RB-1 gene and other loci on chromosome 13, the authors detected a deletion at the RB-1 locus in metastatic SNUC cells that was not present in normal tissue. These findings indicate that somatic mutations at RB-1 locus may be involved in the formation or progression of ectodermal tumors.
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PMID:Possible involvement of the retinoblastoma gene in undifferentiated sinonasal carcinoma. 222 92

We present a case of multifocal osteosarcoma (MFOS) arising 11.5 years after successful treatment of bilateral retinoblastoma. The clinical, imaging and pathological findings at onset, after therapy, and during follow-up are described. Fluorescent in situ hybridization did not reveal a deletion of the RB-1 retinoblastoma gene, although the presence of an inactivating mutation invisible to this method cannot be ruled out. The MFOS may have been a second multifocal tumor associated with the original retinoblastoma or a post-irradiation sarcoma with extensive metastases.
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PMID:Multifocal osteosarcoma as second tumor after childhood retinoblastoma. 1047 25

Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.
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PMID:Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. 1869 45

The retinoblastoma tumor suppressor gene (RB-1) is a key regulator of cellular senescence. Expression of the retinoblastoma protein (pRB) in human tumor cells that lack it results in senescence-like changes. The induction of the senescent phenotype by pRB requires the postmitotic kinase CDK5, the best known function of which is in neuronal development and postmitotic neuronal activities. Activation of CDK5 in neurons depends on its activators p35 and p39; however, little is known about how CDK5 is activated in non-neuronal senescent cells. Here we report that p35 is required for the activation of CDK5 in the process of cellular senescence. We demonstrate that: (i) p35 is expressed in osteosarcoma cells, (ii) p35 is required for CDK5 activation induced by pRB during senescence, (iii) p35 is required for the senescent morphological changes in which CDK5 is known to be involved as well as for expression of the senescence secretome, and (iv) p35 is up-regulated in senescing cells. Taken together, these results suggest that p35 is at least one of the activators of CDK5 that is mobilized in the process of cellular senescence, which may provide insight into cancer cell proliferation and future cancer therapeutics.
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PMID:p35 is required for CDK5 activation in cellular senescence. 2018 42