Adenocarcinoma of pancreas and duodenum associated with cutaneous neurofibromatosis.
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Adenocarcinoma↗
Biomedical subjects
M Oren
Publications and source records attributed to M Oren.
Activated Ha-ras can cooperate with defective simian virus 40 in the transformation of nonestablished rat embryo fibroblasts.
We studied the ability of activated Ha-ras to cooperate with simian virus 40 (SV40) in the transformation of nonestablished rat embryo fibroblasts. Cotransfection with Ha-ras greatly accelerated the rate of focus induction by wild-type SV40. Moreover, a series of transformation-defective SV40 mutants could be partially complemented by Ha-ras. This was true not only for mutants retaining an intact N-terminal immortalization-competent domain, but also for a nonkaryophilic SV40 mutant. In the latter case, all detectable T antigen was cytoplasmic, indicating that efficient transformation can be achieved through the interaction of two nonnuclear proteins. By employing cell lines derived with various SV40 mutants, it was determined that the ability to complex with p53 depends on the integrity of a relatively large region in the C-terminal half of large T. Finally, we report that nonkaryophilic SV40 large T forms a complex with the major heat shock protein HSP70, and we discuss its possible implications.
Animals↗
Effects of the components of breast milk on mucosal enzyme activity of the newborn small intestine.
The effects of the aqueous phase of human breast milk on the disaccharidase activity of newborn rabbit small intestinal mucosal explants were studied in vitro culture. These explants continuously synthesized protein and normal morphology was maintained for the duration of the cultures. Addition of the aqueous phase resulted in significant increase of lactase (p less than 0.001) and maltase (p less than 0.01) concentrations in these organ cultures. This effect was dose dependent and was observed whether the organ biopsies were derived from fed or starved newborn rabbits. Further purification of the aqueous phase showed that the active ingredient exerting these effects was lactose. These studies suggest that lactose may have an important function in stabilization of newborn intestinal disaccharidase enzymes.
Animals↗
Inhibition of cell growth mediated by plasmids encoding p53 anti-sense.
p53 is an oncogene product which has been shown to be directly involved in malignant transformation. Furthermore, it has been proposed that this protein plays an essential role in the control of cell proliferation. In the present study, we investigated the involvement of p53 in growth regulation of cells by employing anti-sense RNA methodology to inhibit p53 expression. Transfection with p53-specific constructs spanning the entire mRNA molecule or the 5' region of the gene led to reduced p53 protein synthesis. Clones derived from such transfected cells exhibited a slower rate of DNA synthesis, as assayed by incorporation of [3H]thymidine. In most cases, transfection of plasmids encoding anti-sense RNA eventually brought about the complete cessation of cell proliferation. No such effects were observed in L12 cells, which do not synthesize p53 and therefore do not depend on p53 expression for their growth, thus excluding the possibility of a non-specific toxic effect exerted by the anti-sense p53 RNA. These findings support the notion that p53 is essential for continuous cell proliferation.
Animals↗
Primary Hodgkin's disease of the spleen.
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Female↗
Co-operation between the p53 protein tumor antigen and platelet-poor plasma in the induction of cellular DNA synthesis.
Plasmids containing DNA sequences coding for p53 were microinjected into quiescent Swiss 3T3 cells. Three constructs were used, carrying either the whole gene sequence, a full-length cDNA, or a hybrid between the gene and the cDNA. All of them stimulated DNA synthesis when cells were incubated with platelet-poor plasma (PPP) following injection. The p53 gene stimulated DNA synthesis to a lesser extent, also in the absence of PPP. Several negative results were obtained with different plasmids, including deletion mutants in the p53 coding region. However, a deletion mutant in which the p53 reading frame ended in the middle of the coding part of the p53 gene still stimulated DNA synthesis in co-operation with PPP. The stimulation of DNA synthesis induced by p53 cDNA was more synchronous and more limited than that induced by serum. The present data suggest that p53 may act as a competence factor in cell cycle progression.
Animals↗
Structure and activity of the translocated c-myc in mouse plasmacytoma XRPC-24.
In the mouse plasmacytoma XRPC-24 both c-mos and c-myc are rearranged. We cloned the rearranged c-myc and found that it was translocated to the immunoglobulin C alpha locus. The breakpoint is at the end of exon 1 in c-myc and approximately 0.5 kb upstream from exon 1 of C alpha. The cloned translocated c-myc linked to a strong transcriptional promoter can efficiently transform rat embryo fibroblasts when co-transfected with the activated Ha-ras. The transformed cells are tumorigenic in syngeneic rats.
Animals↗
Overproduction of protein p53 contributes to simian virus 40-mediated transformation.
The possible involvement of p53 overproduction in simian virus 40 (SV40)mediated transformation was studied by using the rat embryo fibroblast focus formation assay. Transformation by wild-type SV40 was enhanced two- to threefold by cotransfection of a plasmid overexpressing mouse p53. More significantly, such a plasmid could partially complement a transformation-defective deletion mutant of SV40. Hence, the ability of SV40 T antigen to induce high p53 levels may indeed be directly relevant to the viral transforming potential.
Animals↗
[Multiple primary retroperitoneal liposarcoma].
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Adult↗
Torsion of leiomyosarcoma of Meckel's diverticulum.
A rare case report of leiomyosarcoma of Meckel's diverticulum, which caused torsion and strangulation of the diverticulum, is presented. The clinical picture was similar to acute appendicitis, which was the working diagnosis when the 42-yr-old Arab woman was sent to surgery. Although rare, leiomyosarcoma is the most common tumor of Meckel's diverticulum, and has to be considered in the differential diagnosis of right lower abdominal pain.
Abdomen, Acute↗
The 5' region of the p53 gene: evolutionary conservation and evidence for a negative regulatory element.
The 5' regions of the mouse, rat and human functional p53 genes were isolated and analysed. All three genes possess a non-coding exon, comprising exclusively 5' untranslated sequences. This exon contains extensive diad symmetry near the 5' end of p53 mRNA, possibly allowing for the formation of a stable hairpin structure in this mRNA. The nucleotide sequence within this hairpin element is highly conserved among the species. A DNA stretch of 225 bp preceding the p53 mRNA cap site possesses distinct promoter activity when assayed in the CAT system. However, this activity is practically abolished when further upstream p53 sequences (approximately 120 bp) are included in front of the CAT gene. This suggests that the control of p53 gene expression is complex and involves a negative regulatory element.
Animals↗
The p53 cellular tumor antigen: gene structure, expression and protein properties.
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Amino Acid Sequence↗
Human p53 cellular tumor antigen: cDNA sequence and expression in COS cells.
A 2.5-kb cDNA clone for human p53 tumor antigen has been isolated. This clone contains the entire coding region including 135 bp upstream of the first ATG. Comparison of the nucleotide sequence of human p53 and mouse p53 demonstrates that the first ATG in human p53 corresponds to the second ATG (codon No. 4) in mouse p53. The human p53 comprises 393 residues and is longer than the mouse p53 due to six additional codons present at the region corresponding to exon 4 of the mouse p53 gene. The DNA sequence homology between the coding regions of mouse and human p53 is 81% and the conservation of homology is not equally distributed along the molecule. When inserted into SV40-based expression vectors the human p53 cDNA successfully directs the production of a polypeptide with an apparent mol. wt. of 55 kd which can be precipitated by monoclonal antibodies to p53.
Animals↗
p53 cellular tumor antigen: analysis of mRNA levels in normal adult tissues, embryos, and tumors.
The relative levels of mRNA specific for the mouse p53 cellular tumor antigen were determined in various normal adult tissues, embryos, and tumors. All tumors studied contained concentrations of p53 mRNA well above those present in most normal tissues. Normal spleen, however, had p53 mRNA levels comparable to those found in some tumors, despite the fact that they contained barely detectable p53 protein. This apparent discrepancy was found to be due to the extremely rapid turnover rate of p53 in the spleen (half-life, approximately equal to 6 min). In developing fetuses, a marked reduction of p53 mRNA levels was manifest from day 11 onwards, whereas the levels during organogenesis (days 9 to 11) were comparable to those found in undifferentiated embryonic stem cells and in some tumors.
Animals↗
Analysis of the gene coding for the murine cellular tumour antigen p53.
A genomic clone containing the functional gene for the murine p53 cellular tumour antigen was isolated and structurally characterised. The gene contains at least 11 exons and 10 introns, the first intron possessing a length of 6.1 kb. Attempts to determine the exact 5' end of p53 mRNA were inconclusive, probably due to the presence of a remarkable stem and loop structure (delta G degrees approximately equal to -56 kcal/mol) in the 5' region of the gene. Suggestive similarities were found to exist between p53 and the protein product of the myc oncogene.
Amino Acid Sequence↗
Expression of the mouse p53 cellular tumor antigen in monkey cells.
DNA specific for the murine p53 cellular tumor antigen was linked to the early simian virus 40 promoter and introduced into monkey COS cells either by transfection with recombinant plasmids or by infection with virus. Recipient cells made substantial amounts of a protein apparently identical to mouse p53. Severalfold-larger quantities were detected when cells were transfected with an intron-containing p53-specific segment, as compared with transfection with intronless cDNA. The p53 encoded by the recombinant DNA was capable of complexing with the simian virus 40 T antigen. Transfected p53 was also probably associated with a cellular 68-kilodalton protein, which may be related to a protein coprecipitating with p53 in some transformed cells. These findings confirm the predicted reading frame and protein boundaries and demonstrate that apparently functional p53 can be produced in cells via experimentally introduced recombinant DNA.
Animals↗
Abelson murine leukemia virus-transformed cells that lack p53 protein synthesis express aberrant p53 mRNA species.
Cells of the Abelson murine leukemia virus-transformed line L12 that lack the p53 protein also lack polyadenylated mRNA capable of directing the synthesis of p53 in a cell-free system. Direct analysis of stable polyadenylated mRNA from a variety of cell lines shows that all p53 producers shared a common mRNA species (2.0 kilobases) which hybridized with a p53-specific cDNA probe. This species, which appears to be the mature, normal-sized p53 mRNA, was totally undetectable in L12 cells, which did not produce p53 in vivo. However, L12 cells contained two major p53-specific mRNA species of a substantially larger size (3.5 and 6.5 kilobases) than the p53-specific mRNA in the p53-producing cells. Genomic DNA analysis uncovered an apparent alteration in the 5' proximal part of only one p53 gene, which is unique to the L12 cell line. It is thus possible that the nonproducer phenotype of L12 cells is due at least in part to an alteration within a p53-specific DNA sequence. These findings define a system in which production of p53 appears to be efficiently regulated at the level of stable mRNA and which can be used to study the mechanisms controlling p53 expression in Abelson murine leukemia virus-transformed cells.
Abelson murine leukemia virus↗
The gene and the pseudogene for mouse p53 cellular tumor antigen are located on different chromosomes.
The chromosomal assignments of the two genes encoding the murine p53 cellular tumor antigen were determined by using a panel of mouse-Chinese hamster somatic cell hybrid clones and a mouse p53-specific cDNA clone. One gene, probably the functional member of the family, was found to be on chromosome 11. The other gene, which is probably a processed pseudogene, was assigned to chromosome 14. The potential relevance of these findings to documented cases of chromosome 11 trisomy are also discussed.
Animals↗