Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been shown recently that the c-mos oncogene becomes activated in myeloma XRPC-24 via insertion of an intracisternal A particle (IAP) long terminal repeat (LTR). The inserted LTR serves as a promoter from which transcription of the 3' rearranged c-mos initiates. The insertion is in a head-to-head orientation such that the transcriptional orientations of the IAP and the 3' rearranged c-mos are opposite. It has already been shown that this IAP LTR has two promoters, one transcribing the IAP genome and the other transcribing the rearranged c-mos. Since the IAP genomes are actively transcribed in mouse myelomas but not in normal cells, it was interesting to test whether transcriptional activation of the IAP occurs in the presence of active oncogene products, especially nuclear ones. The 5' LTR of the IAP inserted in myeloma XRPC-24 was chosen as a convenient model to test the effect of viral and cellular oncogene products. These included simian virus 40 (SV40) large-T antigen, the adenovirus early 1A (E1A) gene product, the myc gene product, and p53. The LTR was coupled to the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in two orientations, and the levels of CAT directed by the LTR promoters were assayed in either the presence or the absence of the oncogene products. The levels of CAT directed by the 5' LTR promoter transcribing the IAP were significantly elevated in the presence of SV40 large-T antigen, the adenovirus E1A and myc gene products, and p53. The promoter transcribing the rearranged c-mos was transactivated by SV40 large-T antigen and the adenovirus E1A gene product. The results indicate that oncogene products may have an important role in turning on promoters of other genes. The IAP LTR may serve as a useful model for studying the effect of various gene products on promoters which are known to be activated in the malignant state.
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PMID:The long terminal repeat of the intracisternal A particle as a target for transactivation by oncogene products. 293 1

Monoclonal antibodies were raised against a cell surface glycoprotein (46K antigen) expressed by a Moloney sarcoma virus (Mo-MSV)-transformed STU mouse cell line (Sac). Although non-productively transformed Sac cells expressed the 46K antigen at their surface, transplantation of Sac non-producer cells into immunocompetent mice failed to induce anti-46K antibody production. Only transplantation of helper virus-superinfected Sac cells led to the development of anti-46K antibodies in addition to antibodies against helper virus structural antigens. Hybridomas producing anti-46K antibodies were established by fusion of mouse myeloma cells with spleen cells taken from mice bearing Sac tumour cells infected with Moloney helper virus. The monoclonal antibodies were subsequently tested against STU mouse transformants [spontaneously transformed or experimentally transformed with the progressor strain of Mo-MSV and the chemical carcinogen 3-methylcholanthrene (MCA), respectively] and BALB/c mouse transformants [transformed with Mo-MSV, simian virus 40 (SV40) or MCA]. Only one of the transformed cell lines tested, a non-producer transformant (PV-TC-77) induced with the progressor strain of Mo-MSV in an STU mouse was found to express a 46K antigen on the cell surface. The 46K surface antigen expressed by PV-TC-77 cells exhibited the same serological, biochemical and biological properties as the 46K Sac cell surface antigen. Though detectable on the surface of PV-TC-77 non-producer cells, immunocompetent syngeneic recipients of non-producer PV-TC-77 cells remained unresponsive against their 46K surface antigen. Only transplantation of helper virus-infected PV-TC-77 producer cells led to antibody development against the 46K surface antigen.
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PMID:Monoclonal antibody detects a common surface antigen on two independently established murine Moloney sarcoma virus non-producer transformants. 299 78

Mammalian DNA contains several families of highly repeated sequences, some of which have been suggested to be mobile elements. We have screened tumour tissue for the rearrangement of cellular oncogenes and found evidence for the behaviour of repetitive DNA sequences as transposable elements which may activate oncogenes. In the mouse myeloma NSI and XRPC24 we found that intracisternal A particle genome was inserted into the coding region of c-mos. In both cases the rearranged c-mos was transcriptionally activated and was also able to transform NIH 3T3 cells. In the canine transmissible venereal tumour we found that c-myc was rearranged due to the insertion of an 1.8 kilobase pair cellular DNA. Nucleotide sequence analysis demonstrated that the inserted piece is 60% homologous to the monkey KpnI element which is a representative of the LINE group.
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PMID:Activation of oncogenes by transposable elements. 302 23

In the mouse myeloma XRPC-24 the DNA of an intracisternal A-particle (IAP) is inserted within the coding region of c-mos. This insertion splits the c-mos into a 3' rc-mos and a 5' rc-mos separated by approximately 4.7 kb of IAP DNA. The insertion is in a head-to-head orientation and brings the 5' LTR of the IAP in juxtaposition to the 3' rc-mos such that the IAP and the 3' rc-mos are transcribed in opposite directions. The intact c-mos gene is usually dormant, whereas the 3' rc-mos is actively transcribed and is capable of transforming NIH3T3 cells. In an effort to understand the nature of this activation we mapped the 5' ends of the 3' rc-mos mRNA present in XPRC-24. We found two main mRNA start sites, one mapping to the junction of the 3' rc-mos and the 5' LTR, and the other located 10 nucleotides upstream to this junction, within the 5' LTR. This result indicates that the 3' rc-mos in XRPC-24 was activated by insertion of a promoter provided by the LTR of an IAP genome. Furthermore, the 5' LTR appears to possess promoter activities in two directions. This conclusion was confirmed by the fact that this 5' LTR, in both orientations, was able to activate the bacterial gene coding for chloramphenicol acetyltransferase (CAT) in the modular vector pSVOCAT.
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PMID:Mechanism of activation of the mouse c-mos oncogene by the LTR of an intracisternal A-particle gene. 609 57

The cellular oncogene c-mos is rearranged in a mouse myeloma and the tumour mRNA contains transcripts hybridizing with a v-mos probe. The rearranged gene (rc-mos) was cloned in lambda phage and shown to transform mouse fibroblasts in transfection assays, rc-mos differs from its progenitor, c-mos, only at the 5' end of the gene, where c-mos sequences have been substituted by a novel cellular DNA fragment. This fragment contains a 159-base pair (bp) insertion sequence (IS)-like element localized immediately 5' to the junction with c-mos. This is the first demonstration in a non-virally-induced tumour of activation of a cellular oncogene by a mechanism possibly involving DNA transposition.
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PMID:Activation of a cellular oncogene by DNA rearrangement: possible involvement of an IS-like element. 629 37

Studies of a number of normal and carcinogen-transformed murine cell lines, and a variety of murine tissues, have indicated that, in contrast to several other cellular oncogenes, the oncogene c-mos gene is usually transcriptionally silent. The recent report by Rechavi et al. indicating that in the mouse myeloma XRPC24 originally induced by pristane (2,6,10-14-tetramethylpentadecane) the c-mos gene is rearranged and transcriptionally active, and that it can transform murine fibroblasts in a transfection assay, is therefore of considerable interest. Here we show that the c-mos locus has undergone a similar rearrangement, and is also transcriptionally active, in the cell line P3-X63-Ag8-653, a derivative of the mouse myeloma MOPC 21 which was induced by mineral oil. This line is widely used for making hybridomas that synthesize monoclonal antibodies. We also demonstrate that the rearranged c-mos sequence is maintained in three different hybridomas derived by fusion of this cell line with normal murine spleen lymphocytes, suggesting that it may play a role in the continuous growth and/or constitutive immunoglobulin production by these hybridomas.
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PMID:Rearranged c-mos locus in a MOPC 21 murine myeloma cell line and its persistence in hybridomas. 665 82

Recently, some of us reported the detection and molecular cloning of a rearranged cellular oncogene, designated rc-mos, from a non-virally-induced mouse myeloma, XRPC24. Recombinant lambda phage DNA containing the rc-mos gene was active in transforming NIH 3T3 cells in a transfection assay, whereas recombinant DNA containing the unrearranged c-mos gene was not. In rc-mos, coding sequences from the 5' end of c-mos were found to have been displaced by a novel cellular element whose nucleotide sequence was reported. We now document the fact that a 349-base pair (bp) segment of the novel DNA immediately adjacent to the retained c-mos sequences in rc-mos has close homology with the long terminal repeat (LTR) of a known intracisternal A-particle gene. This homology was mentioned in Nature recently after it had been brought to the attention of the editors (N. Hozumi and R. Hawley, personal communication).
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PMID:Homology between an endogenous viral LTR and sequences inserted in an activated cellular oncogene. 683 85