Showing papers by "Carlo M. Croce published in 1983"

Transcriptional activation of the translocated c-myc oncogene in Burkitt lymphoma

Abstract: We have previously demonstrated that translocations of VH genes from chromosome 14 to chromosome 8 and of the c-myc oncogene from chromosome 8 to chromosome 14 occur in Burkitt lymphomas with the t(8;14) chromosome translocation. An association of the c-myc gene with the Cμ immunoglobulin gene has been observed in some but not all Burkitt lymphomas studied previously. In the present study, we have investigated the organization of the human heavy chain locus and of the c-myc gene in the P3HR-1 Burkitt lymphoma cell line. Becuase mouse/P3HR-1 somatic cell hybrids that retain only the 14q+ chromosome and no other human chromosome contain the human Cμ and Cγ genes but not VH genes, we have concluded that the breakpoint on chromosome 14 in P3HR-1 cells is distal to Cμ and between Cμ and VH. Thus, the breakpoint of human chromosome 14 differs in different Burkitt lymphoma cell lines. We also found that the human c-myc oncogene translocated to chromosome 14 in the P3HR-1 cell line is not recombined with the Cμ gene. The breakpoint on human chromosome 8 may therefore also differ in different Burkitt lymphoma cell lines, because we have observed DNA rearrangement of the c-myc gene with the Cμ gene in only some of the Burkitt lymphoma cell lines studied elsewhere. Interestingly, high levels of transcripts of the c-myc oncogene were observed in Burkitt lymphomas with translocated c-myc oncogenes both rearranged and unrearranged. Therefore, the translocation of a c-myc oncogene to the heavy chain locus on human chromosome 14 is apparently sufficient for its transcriptional activation and may be an essential step in the pathway leading to neoplasia.

Effect of morphine on resistance to infection.

Abstract: Morphine was demonstrated to exacerbate infections. Experiments were performed to evaluate variations of phagocytic physiology during morphine treatment. In mice, morphine drastically reduced reticuloendothelial system activity, phagocyte count, phagocytic index, killing properties, and superoxide anion production in polymorphonuclear leukocytes and macrophages. Similar effects on alveolar macrophage count, phagocytosis, and killing were found in rabbits, a result which suggested a lack of species specificity. Additional experiments demonstrated that morphine (1) induces a reduction of lymphoid organ weight, (2) impairs the ability to eradicate infections and (3) is counteracted in its depressing activity on phagocytic physiology by small amounts of Corynebacterium parvum. The results suggest that there is a close relationship between the fact that morphine exacerbates infections and the fact that morphine depresses phagocytic functions; therefore, the negative effect of morphine on phagocytosis is at least one of the reasons for its negative effect on the development of infections.

Transcriptionally active c-myc oncogene is contained within NIARD, a DNA sequence associated with chromosome translocations in B-cell neoplasia.

Abstract: NIARD (non-immunoglobulin-associated rearranging DNA) is located on mouse chromosome 15 at the break point of a commonly observed translocation event involving chromosomes 15 and 12 in murine plasmacytomas. The human cellular analogue of the v-myc oncogene of avian myelocytomatosis virus, strain MC-29, is known to reside on the distal end of human chromosome 8 and has been observed to translocate to chromosome 14 in Burkitt lymphomas. Using a cDNA clone specific for the transcript of the human c-myc gene (H c-myc), we show that the mouse c-myc (M c-myc) gene is contained within NIARD. NIARD-associated chromosome translocations occurred 1.3-2 kilobases (kb) 5′ of the mouse c-myc gene where NIARD recombines with the switch region of the Cα immunoglobulin gene in various murine plasmacytomas. The mouse c-myc encoding region within NIARD spanned <2.4 kb of DNA and expressed a low level of a 2.3-kb polyadenylylated RNA in BALB/c spleen. Increased (10- to 20-fold) levels of rearranged mouse c-myc transcripts (i.e., ≈1.8-2.1 kb) were observed in plasmacytomas that have NIARD-associated chromosome translocations. Human c-myc and NIARD probes detected DNA rearrangements of human c-myc in four of seven Burkitt lymphomas. DNA sequences adjacent to the human c-myc gene recombined with the Cμ immunoglobulin gene locus on chromosome 14 in several Burkitt lymphomas. The activation of the c-myc oncogene by chromosome translocation implicates its involvement in B-cell oncogenesis.

The structure and nucleotide sequence of the 5' end of the human c-myc oncogene

Abstract: We have established the structure and nucleotide sequence of the 5' end of the human c-myc oncogene, using a cloned genomic fragment isolated from a fetal liver library (clone lambda MC41) and cloned cDNA from the human leukemic cell line K562. The human c-myc oncogene consists of three exons and two introns. Primer extension of the human c-myc mRNA of three different cell lines and S1 nuclease protection experiments served to establish the position of two transcription initiation sites. The splicing site of the first exon-intron boundary was determined by comparative analysis of the sequences of the genomic and cDNA clones. The first exon contains termination codons in all three reading frames and no translation initiation signals, confirming our previous observation that the c-myc mRNA has a long 5' noncoding sequence. This first exon also was found to be utilized in the formation of c-myc mRNAs in a variety of human cell lines.

Identification of the c-myc oncogene product in normal and malignant B cells.

Abstract: Antiserum to a synthetic peptide corresponding to the carboxyl-terminus of the human c-myc protein immunoprecipitated a 48,000-dalton protein from a number of normal and malignant human and mouse cells. The size of the protein is consistent with the potential coding region predicted from the c-myc nucleotide sequence, and is the same for malignant cells carrying either a rearranged or an unrearranged c-myc oncogene. Because c-myc transcripts are expressed at higher levels in malignant than in normal B cells, it appears that an increased level of the c-myc protein rather than a change in the gene product is the relevant factor in determining transformation.