Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among 21 human mammary tumors analyzed for transforming genes by transfection of NIH/3T3 cells, only DNA of a carcinosarcoma cell line, HS578T, registered as positive. A Harvey (H)-ras oncogene identified in this line was cloned in biologically active form and the activating lesion was identified as a single nucleotide substitution of adenine for guanine in the 12th codon. This results in substitution of aspartic acid for glycine at this position of the p21 coding sequence. Knowledge that this alteration creates a restriction site polymorphism for Msp I/Hpa II in the H-ras protooncogene made it possible to survey for the presence of the activated H-ras allele in normal cells as well as in clonally derived tumor cell lines of the same patient. We demonstrated the presence of unaltered H-ras alleles in normal HS578 cells. In contrast, every clonally derived HS578T tumor cell line analyzed contained the H-ras oncogene possessing the genetic alteration at position 12. These findings establish that activation of this oncogene was the result of a somatic event selected within all HS578T tumor cells.
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PMID:A position 12-activated H-ras oncogene in all HS578T mammary carcinosarcoma cells but not normal mammary cells of the same patient. 608

Primary structural analyses of beta 3-microglobulin isolated from the tumor cell lines EL4.BU (derived from a C57BL/6 mouse) and C14 (derived from a BALB/c mouse) have revealed the presence of an amino acid difference at position 85 of this molecule. beta 2-Microglobulin isolated from histocompatibility antigens of EL4.BU has alanine at this position, whereas that from C14 has aspartic acid. Determination of the sequence of these molecules has employed radiochemical methodology that was developed in studies of murine histocompatibility antigens. The sequence obtained in this study is: Ile - Gln - Lys - Thr - Pro - Gln - Ile - Gln - Val - Tyr - Ser - Arg - His - Pro - Pro - Glu - Asn - Gly - Lys - Pro - Asn - Ile - Leu - Asn - Cys - Tyr - Val - Thr - Gln - Phe - His - Pro - Pro - His - Ile - Glu - Ile - Gln - Met - Leu - Lys - Asn - Gly - Lys - Lys - Ile Pro - Lys - Val - Glu - Met - Ser - Asp - Met - Ser - Phe - Ser - Lys - Asp - Trp - Ser - Phe - Tyr - Ile - Leu - Ala - His - Thr - Glu - Phe - Thr - Pro - Thr - Glu - Thr - Asp - Thr - Tyr - Ala - Cys - Arg - Val - Lys - His - Ala/Asp - Ser - Met - Ala - Glu - Pro - Lys - Thr - Val - Tyr - Trp - Asp - Arg - Asp - Met. Comparison of the sequence of murine beta 2-microglobulin to the sequences reported for the homologues from man, rabbit, and guinea pig indicate identities of 68%, 66%, and 61%, respectively.
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PMID:Complete amino acid sequence of murine beta 2-microglobulin: structural evidence for strain-related polymorphism. 616 97

Antibodies specific for the amino- and carboxy-terminal portions of simian virus 40 large tumor (T) antigen were obtained by immunization of rabbits with synthetic peptides corresponding to these regions. The amino-terminal synthetic peptide has the sequence Ac-Met-Asp-Lys-Val-Leu-Asn-Arg-(Tyr). The tyrosine residue was introduced in order to couple the peptide to bovine serum albumin with bis-diazotized benzidine. The carboxy-terminal peptide has the sequence Lys-Pro-Pro-Thr-Pro-Pro-Pro-Glu-Pro-Glu-Thr. It was coupled to bovine serum albumin with glutaraldehyde. The antisera against both peptides reacted with large T antigen. The specificity of the immune reaction was demonstrated by inhibition experiments using excess synthetic peptides. Furthermore, fragments of T antigen encoded by the nondefective adenovirus 2-simian virus 40 hybrid viruses Ad2+ND2 and Ad2+ND4, which contain the carboxy terminus and lack the amino terminus of large T antigen, were precipitated only with antiserum to the carboxy-terminal peptide. Small T antigen was not precipitated with either serum, suggesting that the amino terminus of small T antigen has a conformation different from that of large T antigen or that it is sterically hindered by a host protein. The procedures used here are of general importance for identification and characterization of gene product.
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PMID:Antibodies specific for the carboxy- and amino-terminal regions of simian virus 40 large tumor antigen. 625 66

We have identified the single phosphorylated tyrosine in p60src, the transforming protein of Rous sarcoma virus, as part of the sequence. NH2-Arg-Leu-Ile-Glu-Asp-Asn-Glu-Tyr(P)-Thr-Ala-Arg-COOH. Therefore, this is a sequence that is recognized efficiently by a tyrosine protein kinase in vivo. Phosphorylation of tyrosine in cellular proteins appears to play a role in malignant transformation by four classes of genetically distinct RNA tumor viruses. Phosphorylated tyrosines in several other proteins resemble of the tyrosine in p60src in that they are located 7 residues to the COOH-terminal side of a basic amino acid and either 4 residues to the COOH-terminal side of, or in close proximity to, a glutamic acid residue. Therefore it is possible that these features play a role in the selection of sites of phosphorylation by some tyrosine protein kinases. However, several clear exceptions to this rule exist.
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PMID:Analysis of the sequence of amino acids surrounding sites of tyrosine phosphorylation. 628 Jan 76

Antiserum against the synthetic peptide Lys-Arg-Ser-Arg-His-Phe, corresponding to the carboxy terminus of polyoma virus medium tumor antigen (medium T antigen), immunoprecipitates a protein of 36,000 daltons from polyoma virus-infected and uninfected cell extracts treated with the sulfhydryl group reagent N-ethyl-maleimide. This protein appears to share an antigenic determinant with medium T antigen that is normally buried inside the protein or covered up by another protein or cellular structure. The two-dimensional tryptic fingerprints of the 36K protein and of medium T antigen are apparently unrelated to each other. Antiserum against the octapeptide Ac-Met-Asp-Lys-Val-Leu-Asn-Arg-Tyr, including the amino-terminal heptapeptide sequence of the simian virus 40 (SV40) large tumor (T) and small T antigens, cross-reacts with polyoma virus large T antigen, which has an identical amino-terminal heptapeptide sequence except that Lys is replaced by Arg and Asn by Ser. The problem of cross-reactivities of antipeptide sera is discussed.
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PMID:Cross-reactivity of antibodies against synthetic peptides. 629 32

A growth hormone releasing factor of a human pancreatic islet tumor (hpGRF) of an acromegalic patient was purified and subjected to Edman degradation in a spinning cup sequencer. Approximately 0.7-1.2 nmol of peptide was applied to the cup without any pretreatment, after coupling to 3-sulfophenyl isothiocyanate or after cleavage with cyanogen bromide, staphylococcal protease, or trypsin. On the basis of the analytical data, the N-terminal sequence of 39 residues is established to be H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn- Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys- Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser- Asn-Gln-Glu-Arg-Gly-. It is proposed that alanine is residue 40 and represents (as free acid) the C terminus of hpGRF. Synthetic hpGRF(1-40)-OH is highly potent in stimulating GH secretion from the rat anterior pituitary in vitro and in vivo. The C-terminal sequence of hpGRF does not appear to contribute significantly to the biologic intrinsic activity and potency of hpGRF, as demonstrated by the fact that the natural product and the synthetic peptides hpGRF(1-40)-OH, hpGRF(1-40)-NH2, and hpGRF(1-29)-NH2 show equivalent in vitro activities. On the basis of sequence homologies, hpGRF is closely related to members of the glucagon secretin family, especially to the porcine gut peptide PHI.
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PMID:Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumor. 629 53

A 16-amino acid peptide, H2N-Arg-Glu-Gln-Thr-Val-Pro-Val-Asp-Leu-Ser-Val-Lys-Arg-Pro-Arg-Cys-COOH (peptide 204), targeted to the common C-terminus of human adenovirus 12 (Ad12) tumor antigens encoded by the E1A 13S mRNA and 12S mRNA, has been synthesized. Antibody prepared in rabbits against peptide 204 immunoprecipitated two proteins of apparent Mr 47,000 and 45,000 from extracts of [35S]methionine-labeled Ad12-early infected KB cells and a 47,000 protein from extracts of the Ad12-transformed hamster cell line, HE C19. Immunoprecipitation analysis of infected and transformed cells labeled with 32Pi showed that both major Ad12 E1A T antigens are phosphoproteins. Immunofluorescence microscopy of Ad12-early infected KB cells with antipeptide antibody showed the site of E1A protein concentration to be predominantly nuclear. E1A proteins were detected by immunofluorescence at 4 to 6 h postinfection and continued to increase until at least 18 h postinfection. Antipeptide 204 antibody was used to analyze the proteins synthesized in Escherichia coli cells transformed by plasmids containing cDNA copies of the Ad12 E1A 13S mRNA or 12S mRNA under the control of the tac promoter (D. Kimelman, L. A. Lucher, M. Green, K. H. Brackmann, J. S. Symington, and M. Ptashne, Proc. Natl. Acad. Sci. U.S.A., in press). A major protein of ca. 47,000 was immunoprecipitated from extracts of each transformed E. coli cell clone. Two-dimensional gel electrophoretic analysis of immunoprecipitates revealed that the T antigens synthesized in infected KB cells, transformed hamster cells, and transformed E. coli cells possess very similar molecular weights and acidic isoelectric points of 5.2 to 5.4.
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PMID:Identification of adenovirus 12-encoded E1A tumor antigens synthesized in infected and transformed mammalian cells and in Escherichia coli. 638 54

Site-specific antibodies to pp60src, the transforming protein of Rous sarcoma virus (RSV), have been prepared by immunizing rabbits with a chemically synthesized pentadecapeptide corresponding to residues 498-512 (Cys-Trp-Arg-Lys-Asp-Pro-Glu-Glu-Arg-Pro-Thr-Phe-Lys-Tyr-Leu) as deduced from the nucleotide sequence of the Prague C src gene. Antibodies specific for the synthetic peptide were purified from immune sera by affinity chromatography on peptide-bound Sepharose and characterized by a number of immunocytochemical techniques. Immunoprecipitation and Western blot analyses of normal and RSV-transformed cell lines revealed that this peptide antibody identified the authentic viral src gene product. This finding was further supported by indirect immunofluorescence on RSV-transformed rat kidney cells. The anti-peptide antibodies produced dramatic intracellular staining patterns characteristic of the src protein. Although able to immunoprecipitate pp60src, in vitro kinase reactions indicated that, unlike sera from RSV-induced tumor-bearing rabbits, the peptide antibody did not serve as a phosphate acceptor in the immunocomplex. Moreover, immunoprecipitates of pp60src prepared from this site-specific immune reagent were unable to phosphorylate exogenously added casein or the synthetic peptide substrate, Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly. In contrast, pp60src-containing immunoprecipitates made from an anti-peptide serum specific for the COOH-terminal six amino acids (residues 521-526), a region only eight amino acids removed, readily phosphorylated both substrates. This evidence indicates that an antibody directed against residues 498-512 neutralizes the kinase activity of pp60src and suggests that this region may be functionally necessary for the tyrosine-specific kinase activity of this transforming protein.
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PMID:Antibodies to a defined region of pp60src neutralize the tyrosine-specific kinase activity. 641 28

Tumor nucleic acids have frequently been found to be deficient in methylated and other modified nucleotides. In particular, cytoplasmic transfer RNAs (tRNAs) from various neoplasms partially lack the hypermodified nucleoside queuosine, a modification specific for anticodons of histidine-, tyrosine-, asparagine-, and aspartic acid-accepting tRNAs. Using aspartate tRNA as an example, we show here that liver mitochondria contain tRNA fully modified with respect to queuosine, while the corresponding tRNA from mitochondria of Morris hepatoma 5123D completely lacks this constituent. The sequences of these tRNAs, which were determined by a highly sensitive 32P-postlabeling procedure entailing the direct identification of each position of the polynucleotide chains, were found to be (sequence in text) Lack of queuosine in the hepatoma mitochondrial tRNA may be due to the inavailability of queuine in the hepatoma mitochondria for incorporation into tRNA or to inhibition of the modifying enzyme, tRNA (guanine)-transglycosylase, in the tumor. Taking into account results of others indicating a possible involvement of the queuosine modification in differentiation of eukaryotic cells, we hypothesize that the queuosine defect may develop at an early stage of carcinogenesis (i.e., during the promotion phase) and be directly involved in abnormalities of mitochondria which have been observed frequently in transformed cells and tumors.
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PMID:Specific lack of the hypermodified nucleoside, queuosine, in hepatoma mitochondrial aspartate transfer RNA and its possible biological significance. 642 54

The hypophysiotropic peptide, growth hormone-releasing factor (GRF), was isolated from human hypothalamic-hypophysial tissues by means of acid extraction, immunoaffinity chromatography, gel filtration, and two steps of reverse-phase high-performance liquid chromatography. Amino acid sequence determination using a gas-phase sequencer and reverse-phase liquid chromatography of the native peptide and its synthetic replicates showed its primary structure to be as follows: H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln -Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser -Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2, which is identical to that of the GRF recently isolated and characterized from a human pancreatic tumor that had caused acromegaly. Human hypothalamic GRF shows major homologies (93%, 89%, and 86%, respectively) when its primary structure is compared to that of the hypothalamic GRF from the porcine, bovine, caprine, and ovine species.
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PMID:Isolation, primary structure, and synthesis of human hypothalamic somatocrinin: growth hormone-releasing factor. 643 6


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