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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have compared the ability of cloned DNAs of HPV16, a human papillomavirus associated with cervical carcinoma, and BPV1, a papillomavirus inducing skin lesions in cattle, to transform murine C127 cells. Unlike BPV1, HPV16 DNA failed to induce foci when C127 cells were transfected and maintained as monolayers; HPV16-transformed C127 cells could only be detected after cotransfection with HPV16 and pSV2neo DNA, selection for resistance to G418, and assay of pooled selectants for colony growth in agar. HPV16 and BPV1 C127 cells differed in terms of the size and morphology of their colonies in agar, but not in their colony-forming efficiencies. In addition, the tumors they induced in nude mice were clearly histologically distinct, with the HPV16 C127 tumors considerably more anaplastic. The HPV16 C127 cells contained viral DNA at high copy numbers integrated at random sites in the C127 genome, while the BPV1 C127, as expected, contained episomal BPV1 DNA molecules. The high complexity of the integrated HPV16 DNA was maintained in the pooled cells grown through extended passage in vitro, in clonal lines derived from single agar colonies, in nude mouse tumors induced by the cells, and in a nude mouse tumor-derived cell line, indicating the stability of the HPV16 sequences in the cells. HPV16 transcripts in the transformed C127 cells were present in three size classes (1.5, 2, and 4 kilobases) on Northern blots. The different transformed phenotypes in the same cell line induced by two structurally similar, yet distinct viruses imply differences in the underlying transforming mechanisms and possible different virus-host cell molecular interactions.
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PMID:Transformation of C127 mouse fibroblasts by human papillomavirus 16. 283 48

Neonatal rat hepatocytes (NRH) in primary cultures were transformed upon transfection with plasmid pSV 5-neo containing polyoma virus (Py) early region sequences. Clones of cells (Py-NRH) resistant to the antibiotic G418 were obtained after selection in arginine-deficient medium with serum, epidermal growth factor (EGF), transferrin and insulin. They did not undergo senescence during serial subcultivation. One clone (Py-NRH Cl A) harbored a single integrated copy of Py early region sequences and expressed transforming Py genes, hepatocyte-specific transcripts, including albumin, alpha-fetoprotein (AFP) and tyrosine aminotransferase (TAT) mRNAs. Subclones isolated after about 45 cell doublings still contained albumin and AFP, but no TAT mRNAs, indicating that long-term stabilization of liver functions is not necessarily permanent unless selected for (e.g. arginine synthesis). Cells grew unrestricted in medium containing insulin and no longer required EGF. Cells grew in agar, secreted a beta-transforming growth factor-like activity into the medium and were tumorigenic in nude mice. Hybridization studies using v-erbB DNA as a probe showed that Py-NRH, unlike neonatal hepatocytes in primary culture, express the EGF receptor gene at low or undetectable levels. Py-NRH Cl A and a subclone (5A) derived from it, however, contained elevated levels of rat c-neu oncogene-related RNA, whereas levels in another subclone (3A) were low or undetectable. These findings demonstrate that a proto-oncogene was activated after transfection of hepatocytes with DNA tumor virus transforming genes. However, the expression of c-neu oncogene is not related to the maintenance of the transformed state.
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PMID:Transformation of differentiated neonatal rat hepatocytes in primary culture by polyoma virus early region sequences. 283 82

Activated ras oncogenes have previously been implicated in the pathogenesis of human lung carcinomas. A v-Ha-ras-containing retrovirus, Zip-ras, was generated by inserting the coding region of the v-Ha-ras oncogene into the Zip-NeoSV(X) [Cepko et al., Cell 37:1053-1062, 1984] retroviral vector. Amphotrophic Zip-ras retrovirus was used to infect an SV40 large T antigen-positive immortalized cell line, BEAS-2B, derived from normal bronchial epithelial cells, the predominant progenitor cells of human lung carcinomas. Zip-ras-infected BEAS-2B cells selected for G418 resistance formed anaplastic carcinomas in 12 of 15 athymic nude mice (latency 3 wk), whereas Zip-NeoSV(X)-infected BEAS-2B control cultures inoculated into 12 nude mice formed no tumors after a minimum of 7 mo. Tumor cell lines were established and demonstrated to be of human epithelial origin and to express v-Ha-ras p21 protein. A common feature of the tumor cell lines was an increase in ploidy. The increased efficiency of neoplastic transformation by v-Ha-ras of cell lines as compared with our previous results with normal bronchial epithelial cells [Yoakum et al., Science 227:1174-1179, 1985] is consistent with the hypothesis that the "immortalization" step is rate-limiting in in vitro human epithelial cell carcinogenesis.
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PMID:Neoplastic transformation of a human bronchial epithelial cell line by a recombinant retrovirus encoding viral Harvey ras. 285 21

A cAMP-resistant mutant (Kin-8) isolated from Y1 mouse adrenocortical tumor cells harbors a specific lesion in the regulatory subunit of the type 1 cAMP-dependent protein kinase. This mutant also is resistant to the effects of corticotropin and cAMP on steroidogenesis, growth and morphology, suggesting an obligatory role for the protein kinase in regulation of adrenocortical functions. In this study, the cAMP-resistant phenotype of the Kin-8 mutant was reverted by transformation with DNA from cAMP-responsive Y1 cells, and the biochemical basis of the transformation was explored. Initially, Y1 mouse adrenocortical tumor cells were evaluated for their competence as recipients in DNA-mediated transformation experiments, by measuring their ability to incorporate and express a bacterial gene (neo) encoding resistance to neomycin. Y1 cells were transfected with the plasmid pSV2-neo (an SV40-neo hybrid vector designed for expression in animal cells) and screened for resistance to the neomycin analog, G418. Neomycin-resistant transformants were recovered from Y1 cells at a frequency of approximately one per 10(3) cells per 10 micrograms of DNA, and had specific neo sequences integrated into their high molecular weight (mw) DNA. The Y1 mutant, Kin-8, then was transformed with pSV2-neo DNA plus high mw DNA prepared from cAMP-responsive Y1 cells. Cells competent for transformation were recovered by selective growth in the neomycin analog G418, and these transformants were screened for recovery of morphological responses to cAMP. Several colonies capable of rounding up in the presence of cAMP were recovered after transformation with DNA from Y1 cells. These transformants also recovered the ability to round up in the presence of corticotropin, and were able to respond to both corticotropin and cAMP with increased steroidogenesis. Transformants generated from either Y1 or Kin-8 cells were unstable. Y1 cells lost resistance to neomycin when grown in the absence of G418 at a frequency of 4% per generation. Similarly, Kin-8 transformants lost their sensitivity to cAMP in subsequent culture passages. In some of the cAMP-responsive transformants, cAMP-dependent protein kinase activity was recovered and approached the activity seen in cAMP-responsive Y1 cells. The recovery of a normal protein kinase by transformation appeared to have been sufficient to reverse the cAMP-resistant phenotype of Kin-8 cells. In other cAMP-responsive transformants, protein kinase activity was not appreciably affected by cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Recovery of hormonal regulation in protein kinase defective adrenal cells through DNA-mediated gene transfer. 300 21

Internal irradiation of mice using bone seeking radionuclides results in the activation of endogenous retroviruses and in the subsequent development of bone tumors. Genomic DNA from an osteosarcoma cell line, derived from an 90Sr-induced bone tumor, was cotransfected with the plasmid pSV2-neo into NIH/3T3 cells and G418-resistant transfectants gave rise to colonies in soft agar. Southern blot analysis of these first cycle transformants revealed the presence of extra copies of c-ras. We have analysed the arrangement of ecotropic murine leukemia proviral sequences in seven 90Sr-induced bone tumors and one osteosarcoma cell line of CF1-mice. Integration of ecotropic and/or ecotropic recombinant proviruses seems to be involved in rearrangements of 3' provirus cellular junction fragments occurring in all tumor DNAs analysed, but no indication for site-specific integration was found. We also determined the primary structure of FBR-MuSV, a transforming retrovirus able to induce bone tumors in newborn mice. FBR-MuSV contains sequences from all four exons of the murine c-fos gene, but lacks sequences encoding the first 24 and the last 98 amino acids of the c-fos gene product. The coding region of FBR-MuSV has also undergone two small in frame deletions. Thus, the v-fosFBR-MuSV retains 236 amino acids of the 380 amino acids of the murine c-fos product. In FBR-MuSV-transformed cells two fos-containing mRNAs have been detected: a 3.3-kb full-size genomic RNA and a 2.2-kb subgenomic mRNA as revealed by both fos- and MuLV-hybridization probes.
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PMID:Oncogene involvement in radiation- and virus-induced mouse osteosarcomas. 301 18

Previous studies have shown that a 558-bp fragment of human cytomegalovirus (CMV) DNA contained within pCM4127 and designated CMV mtr can morphologically transform rodents cells in vitro. By cotransformation with pCM4127 and a plasmid conferring G418 resistance, pSV2neo, morphologically transformed NIH3T3 cell lines were isolated. Dot blot hybridization indicated that approximately 30% of the transformants retained CMV sequences. Two cell lines which retained viral DNA were chosen for further study. They were capable of anchorage independent growth and formed tumors in nude mice. Integrated viral sequences in the transformants and tumor cell lines were analyzed by Southern blotting. A bacteriophage lambda library was constructed using a tumor cell line which retained a single copy of the viral sequences, and a phage was isolated which contained the integrated plasmid and the flanking cellular sequences. A complex rearrangement between pCM4127 and pSV2neo had occurred. DNA sequence analysis showed integration of the plasmid sequences into repetitive mouse DNA and identified an adjacent mouse sequence.
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PMID:Characterization of the integration site of the CMV mtr in a tumor cell line. 302 70

A transforming sequence was identified using co-transfection of DNA from the human mammary carcinoma cell line MCF-7 and of a G418 resistance gene into NIH 3T3 cells, followed by tumor formation in athymic mice. This sequence, named mcf.2, was molecularly cloned. A transforming activity resides in a cosmid clone of 42 kb. mcf.2 did not cross-hybridize with the known oncogenes tested. In situ hybridization localized it on the X chromosome, probably at q27. This localization was confirmed by hybridization to a panel of human--rodent cell line DNAs.
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PMID:Localization of the mcf.2 transforming sequence to the X chromosome. 303 15

We have used deletion mutagenesis to analyze a TR-DNA promoter from the octopine-type Ti plasmid pTiB6806. The promoter for the gene encoding mannopine synthase (mas) was cloned upstream of the bacterial kanamycin-resistance gene neomycin phosphotransferase II (NPT II). Bal31 deletion mutagenesis was used to generate deletion derivatives of the mas/NPTII gene beginning 1353 bp upstream of the initiation of transcription and extending to 120 bp downstream from the mRNA start site. Deletions that left intact 318 bp upstream of transcription initiation had no detectable effect on the ability of tumors harboring the deletion to synthesize correctly initiated mRNA or to grow on the kanamycin analogue G418. Deletion to-138 destroyed the ability of sunflower crown gall tumors to grow on G418 although low levels of the mas/NPTII transcript were detected in one tumor line. Deletions that left only 57 bp upstream of transcription initiation allowed neither growth on G418 nor detectable mas/NPTII synthesis, even though the CCAAT and TATAA homologies were intact. The mas promoter is functional in Agrobacterium tumefaciens and we present data concerning the effects of the Bal31 deletions on the growth of A. tumefaciens on kanamycin.
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PMID:Deletion analysis of the mannopine synthase gene promoter in sunflower crown gall tumors and Agrobacterium tumefaciens. 303 93

This study describes a general strategy to produce hybrid monoclonal antibodies that are capable of targeting human cytotoxic T lymphocytes (CTL) against any cell carrying the appropriate target antigen. This is done by fusing a HAT-sensitive, G418-resistant anti-T3 hybridoma with immune spleen cells (or with other hybridomas) that produce antibodies against the desired target antigen. In the hybrid hybridomas the reassortment of Ig heavy and light chains results in the production of bifunctional antibody molecules. Because of their double specificity, these antibodies are able to bridge human CTL to target cells and trigger cytotoxic function. We have isolated several stable hybrid hybridomas in which one specificity is against T3 and one either against HLA antigens (class II, DC-1, A3), human Ig (IgM, IgE, kappa), Toxoplasma gondii or an ovary carcinoma-associated antigen. In all of these cases we show that culture supernatants can efficiently and specifically target any CTL clone against any target cell that possesses the relevant surface antigen recognized by the antibody. Furthermore, the killing requires as little as 0.1 ng/ml of antibody, occurs at effector to target ratios comparable to those used in conventional cytotoxic assays and does not affect bystander cells. Nonspecific killing of Fc receptor-positive cells can be avoided using F(ab')2 fragments. As an example, we show that it is possible to change the major histocompatibility complex class and allospecificity of a CTL clone and target CTL against non-major histocompatibility complex antigens such as Ig, parasites and tumor-associated antigens.
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PMID:The use of hybrid hybridomas to target human cytotoxic T lymphocytes. 310 50

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld-negative, and two Neor clones were selected by means of a 125I-protein A binding assay using an anti-H-2Ld monoclonal antibody. The antigenic expression of the H-2Ld gene products was only 20-40% on the Ld-positive clones compared with Meth-A tumor cells of BALB/c mice. The 50% lethal tumor dose of these clones in C57BL/6 mice was 5.6 X 10(6) in the Ld-positive clones, but only 1.3 X 10(5) in the 3LL/3 parent clone, 1.2 X 10(5) in the Neor clones, and 2.2 X 10(5) in the Ld-negative clones. The tumorigenicity of the Ld-positive clones was, therefore, reduced to less than 1/40 of that of the parent tumor cells. The decreased tumorigenicity of the Ld-positive clones was abrogated in mice irradiated with 600 rads. After inoculation and spontaneous regression of the viable Ld-positive clone cells, the mice acquired transplantation resistance against the challenge of a parental 3LL/3 tumor. However, the immunogenicity variation between Ld-positive, Ld-negative, Neor, and 3LL/3 parent clones showed no statistical difference. These results indicate that tumor cells transfected with an allogeneic class I H-2 gene can express an H-2 foreign antigen, can regress in syngeneic hosts, and can induce antitumor transplantation resistance against the original tumors, although they are not able to enhance their immunogenicity.
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PMID:Xenogenization of a mouse lung carcinoma (3LL) by transfection with an allogeneic class I major histocompatibility complex gene (H-2Ld). 310 4


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