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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the role of simian virus 40 (SV40) large T and small t antigens in tumorigenesis in animals, we generated transgenic mice which expressed either both the SV40 large T and small t antigens or the SV40 large T antigen alone under the control of the mouse mammary tumor virus long terminal repeat. The mouse mammary tumor virus long terminal repeat directs the expression of transgenes in ductal epithelial cells of several organs, including the mammary gland, lung, and kidney, and in lymphoid cells. The mice which expressed both the T and t tumor antigens developed lung and kidney adenocarcinomas, while those which expressed large T alone did not. Both types of mice developed malignant lymphomas with similar frequencies and latency periods. Our results show that the SV40 small t antigen cooperates with the large T antigen in inducing tumors in slowly dividing epithelial cells in the lung and kidney.
Mol Cell Biol 1988 Aug
PMID:Requirement for the simian virus 40 small tumor antigen in tumorigenesis in transgenic mice. 285 Apr 90

There are now many examples of the successful expression of genes transduced by retroviruses in studies from outside the field of neuroscience. Retroviruses will undoubtedly also prove to be effective tools for neuro-scientists interested in expressing cloned neurotransmitter and receptor genes. There are also other less obvious applications of retroviruses, such as their insertional mutagenic effects, which may be useful in studies of the genetic factors and biochemical mechanisms involved in, for example, neurotoxicity. Strong cellular promoters have been identified by retroviral infection and subsequent rescue of the flanking genomic DNA. Retroviruses can be employed again to reintroduce these regulatory sequences back into cells. In this way the complexities of gene expression in the many subpopulations of neurons may be unraveled. Retroviruses can also serve as very useful genetic markers in studies of development and lineage relationships. Retroviruses may be used to efficiently transfer oncogenes into neuronal cells to create new cell lines. This application exploits one of the natural traits of retroviruses--oncogenesis--which led to their original discovery. Finally, there are neurotropic retroviruses that could serve as important vectors for delivering genes into neurons. Studying these retroviruses may lead to an understanding of how they cause neuropathologic changes in the CNS.
Mol Neurobiol 1988
PMID:Retroviral-mediated gene transfer. Applications in neurobiology. 285 93

The chvB operon of Agrobacterium tumefaciens is required for bacterial attachment to plant cells and for efficient crown gall tumor formation. As defined by the virulence phenotypes of mutants with transposon insertions mapping in the region, the operon was previously mapped to a 5-kilobase (kb) stretch of chromosomal DNA. We report here that the operon is actually about 8.5 kb long and that it contains a 7-kb gene coding for a large membrane protein involved in the synthesis of cyclic beta-1,2-glucan. Mutants with transposon insertions within the 5-kb phenotypically defined operon do not synthesize this functional protein, do not synthesize beta-1,2-glucan, and do not form tumors. However, mutants with insertions that map up to 3.5 kb downstream of the phenotypically defined operon synthesize truncated proteins that are active in beta-1,2-glucan synthesis. These mutants form tumors. The truncated proteins correspond closely in size with the map positions of the insertions, suggesting that the insertions truncate the proteins by translational termination. A plasmid that contains only the phenotypically defined chvB operon also codes for a truncated protein. A fusion product between the protein and beta-galactosidase carried on a Tn3-HoHo1 insertion was observed in one mutant. Partial trypsin digestion of wild-type inner membranes generated truncated proteins that were active in beta-1,2-glucan synthesis, demonstrating that a large portion of the protein is not required for beta-1,2-glucan synthesis. The correlation between beta-1,2-glucan synthesis by the truncated proteins and tumorigenesis strongly implicates the polysaccharide product of this protein in tumor formation.
Mol Plant Microbe Interact 1988 Mar
PMID:Identification of the product of an Agrobacterium tumefaciens chromosomal virulence gene. 285 22

It has been proposed that loss of genes at specific chromosomal loci leads to tumorigenesis in some human tumors. This type of oncogenesis was first demonstrated in retinoblastoma and Wilms' tumor. Recently, it has been reported that acoustic neuroma, ductal breast tumor, and renal cell carcinoma may be caused by the same mechanism. Cytogenetic studies demonstrated that some meningiomas have monosomy of chromosome 22. In addition, human meningiomas are often associated with bilateral acoustic neuroma in which specific loss of alleles on chromosome 22 has been demonstrated. Then, we compared constitutional and tumor genotypes from 14 cases of sporadic human meningiomas, using four polymorphic DNA probes on chromosome 22 (SIS, D22S1, D22S9, IGLC). Loss of constitutional heterozygosity was found in three of 11 informative cases. Two of the three meningiomas maintained constitutional heterozygosity at the IGLC locus and another one showed no loss of heterozygosity at IGLC or D22S9. These results suggest that loss of genes on chromosome 22 caused by either a partial deletion or a mitotic recombination at a locus distal to D22S9 plays an important role in tumorigenesis of the human meningioma.
Mol Biol Med 1988 Feb
PMID:Loss of genes on the long arm of chromosome 22 in human meningiomas. 263 83

Epidermal growth factor (EGF) receptor is expressed selectively by human melanoma cells which show the presence of an extra copy of chromosome 7. None of the cells of benign pigmented lesions (nevi) or radial growth phase (nonmetastatic) primary melanoma expressed EGF receptor and none of these cells showed an extra copy of chromosome 7. The results indicate that a single extra dose of a gene (for EGF receptor) may provide a selective advantage to cells in the late stages of tumorigenesis.
Somat Cell Mol Genet 1985 May
PMID:Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. 298 38

MCF-7 human breast cancer cells have been studied for hormonal regulation of secretion of an insulin growth factor-I (IGF-I)-related growth factor. 17 beta-Estradiol, which is required for tumorigenesis of the cell line in the nude mouse and which stimulates proliferation in vitro, was able to significantly induce IGF-I secretion at 10(-13) M, with maximal induction at 10(-11) M. Under optimal conditions IGF-I could be induced 4-fold after 4 days. Demonstration of estrogenic stimulations required removal of phenol red, a weak estrogen, from the cell culture medium. In addition to estrogen, insulin, epidermal growth factor, and transforming growth factor alpha induce both cellular proliferation and IGF-I secretion, while growth inhibitory antiestrogens, transforming growth factor beta, and glucocorticoids have the opposite effect. In each case, modulations in IGF-I secretion preceeded effects on cellular proliferation. IGF-I was not regulated by human GH, basic fibroblast growth factor, platelet-derived growth factor, or PRL, none of which affected proliferation rate. Thus, regulation of IGF-I secretion in human breast cancer is controlled by different hormones from those previously reported in human fibroblasts. Regulation of IGF-I by neither estrogen nor antiestrogen was associated with changes in steady-state mRNA levels; thus regulation may occur at a step beyond mRNA. We conclude that IGF-I production is tightly coupled to growth regulation by estrogens, antiestrogens, and other hormones and may contribute to autocrine and/or paracrine growth regulation by these agents in breast cancer.
Mol Endocrinol 1988 Mar
PMID:Multihormonal regulation of insulin-like growth factor-I-related protein in MCF-7 human breast cancer cells. 304 Dec 62

The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, which are benign and self-regressing skin tumors, both in humans and in a corresponding animal model system. Keratoacanthomas were induced on rabbit ears by repeated applications of 7,12-dimethylbenz(a)anthracene. About 60% of the tumor DNAs produced transformed foci after transfection into NIH 3T3 cells, and in all of them the transforming gene was identified as H-ras by Southern and Northern (RNA) hybridization. Immunoprecipitation experiments suggested that the transforming rabbit H-ras protein carried a mutation in codon 61. In addition, an activated H-ras gene was detected in a human keratoacanthoma by using a nude mouse tumorigenesis assay after transfection of tumor DNA into NIH 3T3 cells. This is the first report of ras activation in a benign human tumor. The transforming human H-ras gene showed a point mutation in codon 61 that would result in leucine instead of the glutamine present in the normal gene product. The finding of ras activation in tumors that are not only benign but also self-regressing indicates that activated ras genes are not sufficient to maintain a neoplastic phenotype, although they likely play a role in early stages of tumorigenesis.
Mol Cell Biol 1988 Feb
PMID:H-ras activation in benign and self-regressing skin tumors (keratoacanthomas) in both humans and an animal model system. 312 91

We examined the mechanisms that control the downregulation of the c-myc mRNA during differentiation of HL60 cells. On treatment with dimethyl sulfoxide, HL60 cells downmodulated their steady-state c-myc message levels, ceased to proliferate, and underwent terminal differentiation. In nuclear run-on assays in which distinct segments of the c-myc gene were used as probes, an increased blocking to elongation of nascent c-myc transcripts was shown during the early phase of differentiation. During a later phase, however, a loss of transcriptional initiation was observed. This loss of promoter activity correlated well with dramatic changes in the chromatin structure of the c-myc gene, as determined by DNase I-hypersensitive site analysis. In particular, two hypersensitive sites near the two major c-myc promoters disappeared at the time that promotion abated. The newly described, later-acting negative transcriptional control of c-myc also correlated temporally with the inability to reverse the downregulation of the c-myc message quickly on withdrawal of the differentiating agent. Therefore, a terminal step during differentiation may be linked to the later-acting mode of transcriptional regulation of c-myc. The evidence presented in this report has implications for tumorigenesis in Burkitt lymphomas, in which the germ line, nontranslocated c-myc allele is transcriptionally silent.
Mol Cell Biol 1988 Feb
PMID:Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells. 316 50

We have surveyed a panel of induced murine lymphomas for c-ras gene mutations. The K-ras gene seems to be preferentially activated in our system, and there are at least two examples of concomitant K- and N-ras gene mutations in the same tumor. This indicates that in some cases additional ras mutations may contribute to tumorigenesis and is evidence for a role of ras activation in tumor progression.
Mol Cell Biol 1988 May
PMID:Concomitant K- and N-ras gene point mutations in clonal murine lymphoma. 329 Jun 53

Many highly homologous genes are present in the murine major histocompatibility complex (MHC) class I gene family. Consequently, it is difficult to distinguish between RNA transcripts of individual class I genes solely on the basis of nucleic acid hybridization analysis using DNA probes over 50 base pairs long. To avoid this problem, I have designed and synthesized a set of oligonucleotide probes capable of detecting transcripts of single class I genes in the MHC of C57BL/10 mice or sets of allelic class I genes at the same genetic locus in MHC disparate mouse strains. Using these probes, it is possible to determine the relative abundance of specific class I gene transcripts in a wide variety of cell and tissue types from inbred or MHC disparate mice. Examples of the use of these probes to detect different class I gene transcripts in cloned murine T cells, T cells transformed with Radiation Leukemia Virus, chemically induced thymoma cell lines and embryonic tissues are described. The results of these experiments are discussed in the light of possible roles of class I antigens in tumorigenesis or in early development.
Mol Cell Probes 1987 Sep
PMID:Analysis of major histocompatibility complex class I gene transcription using oligonucleotide probes. 350 10


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