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A Corallini

Publications and source records attributed to A Corallini.

At least 19 recordsLinked to original sources
PubMed1992

Suppression of tumorigenicity and anchorage-independent growth of BK virus-transformed mouse cells by human chromosome 11.

Viral transformation models may be useful for detecting and mapping human tumor suppressor genes. BK virus (BKV), a human papovavirus, readily transforms rodent cells but is unable to transform human cells, suggesting that oncosuppressive functions expressed in human cells control BKV oncogenic activity. We have transferred human chromosome 11 to BKV-transformed mouse cells. All of the cell clones were suppressed in the tumorigenic phenotype and anchorage-independent growth, except one clone which was nontumorigenic but maintained the ability to grow in soft agar. Cytogenetic analysis and DNA hybridization with chromosome 11-specific probes showed that all the reverted hybrids had an intact human chromosome 11, except the clone growing in semisolid medium which had lost the short arm. The results suggest that a gene located on 11p controls anchorage independence, whereas a gene on 11q controls the tumorigenicity of BKV-transformed cells. BKV T-antigen was expressed in all the hybrid clones at the same level as in the parental cell line, indicating that the putative human tumor suppressor gene(s) do not inhibit expression of the viral oncogene and must operate by another mechanism in inducing reversion of the oncogenic phenotype. Since BKV-transformed mouse cells are highly susceptible to retrovirus infection, this model can be used for searching and cloning tumor suppressor gene(s) by retrovirus-mediated "insertional mutagenesis".

Animals↗
PubMed1990

Characterization of BK virus variants rescued from human tumours and tumour cell lines.

Episomal BK virus (BKV) DNA was detected in primary human brain tumours, in Kaposi's sarcoma and in cell lines from brain tumours. Ewing sarcoma and osteogenic sarcoma. Infectious BKV was rescued from several tumours and tumour cell lines by transfection of total cellular DNA into human embryonic fibroblasts. Restriction endonuclease and nucleotide sequence analysis showed that all the rescued viruses are similar to BKV-IR, a BK variant previously isolated from a human tumour of pancreatic islets, indicating that a specific BKV strain may be associated with certain types of human tumours. All the variants contain a putative transposable elements in the regulatory region of the viral genome. This region has mutagenic properties and enhancing activity in transformation, suggesting a possible role of these variants in tumour induction or progression.

Animals↗
PubMed1988

Co-operation in cell transformation between BK virus and the human c-Harvey-ras oncogene.

Early-passage hamster embryo cells were transformed by recombinant DNA molecules containing BK virus (BKV) early-region gene and either the activated c-Ha-ras oncogene (pBK/c-rasA) or the normal c-Ha-ras proto-oncogene (pBK/c-rasN). The recombinant DNAs had a greater transforming ability and converted hamster cells to a more malignant phenotype than the single genes transfected separately. pBK/c-rasA was significantly more powerful than pBK/c-rasN in conferring to cells all the characteristics of transformation. Transfected DNA sequences were integrated mostly as single insertions into cellular DNA. Specific c-Ha-ras and BKV transcripts as well as c-Ha-ras p21 and BKV T antigen were detected in transformed cells. Although stimulation of c-Ha-ras expression by BKV enhancers cannot be excluded in recombinants, super-transfection and co-transfection experiments in hamster embryo cells and pre-neoplastic cell lines showed that BKV early-region and c-Ha-ras co-operate in transformation by contributing separate and independent functions.

Animals↗
PubMed1988

Factors affecting amplification of BK virus episomal vectors in human cells. Brief report.

Analysis of factors determining replication of BK virus (BKV) episomal vectors in human cells showed that vector copy number was related to the level of BKV T antigen expression. T antigen was synthesized efficiently, as assessed by indirect immunofluorescence, in vector-transfected primary embryonic fibroblasts undergoing neoplastic transformation. Surprisingly, transfected continuous cell lines (143 B, HeLa and KB), kept under biochemical selection or tested in transient assays, produced negligible amounts or no T antigen, revealed only by a sensitive ELISA test, suggesting that in these cells vector amplification was under the control of cellular factors. Presence or absence of BKV late region sequences, BKV strain, orientation of the inserted genes and presence or absence of selection were not relevant for vector replication. Type of biochemical selection, however, was important, since BKV vectors containing the thymidine kinase gene replicated better than those containing the neo gene. Despite great variability, vector copy number increased in transfected clones of adenovirus 5-transformed 293 cells, in the absence of immunofluorescence detectable T antigen. These cells express adenovirus immediate early proteins E1A and E1B which may directly or indirectly activate BKV origin of replication.

Antigens, Polyomavirus Transforming↗
PubMed1988

Cooperation in oncogenesis between BK virus early region gene and the activated human c-Harvey ras oncogene.

Rapidly growing, undifferentiated brain tumours were induced in newborn Syrian hamsters by intracerebral inoculation of a recombinant DNA (pBK/c-rasA) carrying the BK virus (BKV) early region gene and the activated human c-Harvey-ras (c-Ha-ras) oncogene. Neither of the two genes inoculated alone nor recombinant DNA of the BKV early region gene and the normal human c-Ha-ras proto-oncogene were tumourigenic. Tumour-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumours and tumour cell lines contained pBK/c-rasA sequences integrated into cellular DNA and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T antigen and c-Ha-ras p21. These findings are discussed in relation to a possible cooperation or synergism between BKV and cellular oncogenes in human neoplasia.

Animals↗
PubMed1987

Induction of malignant subcutaneous sarcomas in hamsters by a recombinant DNA containing BK virus early region and the activated human c-Harvey-ras oncogene.

Malignant undifferentiated sarcomas were induced in 11 of 15 (73.3%) newborn Syrian hamsters by s.c. inoculation of a recombinant DNA (pBK/c-rasA) containing BK virus (BKV) early region gene and the activated human c-Harvey-ras(c-Ha-ras) oncogene derived from T24 bladder carcinoma. The two genes inoculated independently as well as a recombinant DNA of BKV early region gene and normal human c-Ha-ras proto-oncogene were not tumorigenic. Tumor-derived cell lines propagated in culture were immortalized and had growth characteristics consistent with a fully transformed phenotype. Tumors and tumor cell lines showed tandem insertions of pBK/c-rasA in high copy number and expressed BKV- and c-Ha-ras-specific transcripts as well as BKV T-antigen and c-Ha-ras protein with a molecular weight of 21,000. We conclude that BKV DNA requires interaction with other oncogenic functions for tumorigenicity. These findings may be relevant to the role of BKV in human neoplasia, where cooperation or synergism between BKV and cellular oncogenes could occur as an aspect of the multifactorial process of carcinogenesis.

Animals↗
PubMed1987

Association of BK virus with human brain tumors and tumors of pancreatic islets.

BK virus (BKV) DNA was detected by Southern blot hybridization in 19 out of 74 (25.6%) human brain tumors and in 4 out of 9 (44.4%) human tumors of pancreatic islets. BKV DNA was free, in an episomal state and generally in a low copy number (0.2 to 2 genome equivalents per cell). Only occasional tumors contained 10 to 20 genome copies per cell. Viral DNA sequences integrated into cellular DNA were not detected. A number of tumors expressed BKV-specific RNA and T antigen. By transfection of total tumor DNA into human embryonic fibroblasts, viruses with the biological and antigenic properties of BKV were rescued from 6 brain tumors and from 2 tumors of pancreatic islets. Restriction endonuclease mapping of the genomes of the rescued viruses showed that they differ from wild-type BKV. They are all similar to each other and to BKV-IR, a virus previously rescued from a human tumor of pancreatic islets, suggesting the possible association of a BKV variant with specific types of human neoplasms. The significance of the relationship of these BKV variants to human tumors and their possible etiologic role in human oncogenesis are discussed.

Adenoma, Islet Cell↗
PubMed1986

Molecular and biological properties of BK virus-IR, a BK virus variant isolated from a human tumor.

We describe the molecular and biological properties of BK virus (BKV)-IR, a new BKV variant isolated from a human tumor of pancreatic islets. BKV-IR bears a 253-base-pair (bp) deletion and an 80-bp insertion in the early region of the genome. The deletion abolishes the expression of small-t antigen. The inserted sequences, grouped in four clusters, produce rearrangements in the first and second enhancer elements. They are bound by 12-bp direct repeats and could form a 217-base stem-loop structure suggestive of an insertion sequence. As compared with wild-type BKV, BKV-IR transformed hamster cells with a reduced efficiency and induced ependymomas in hamsters at a lower frequency and with a longer latency period. Tumors induced by BKV-IR, however, showed features of higher malignancy. The possible role of the insertion sequence-like element in transformation by BKV-IR is discussed.

Adenoma, Islet Cell↗
PubMed1985

Histologic, immunofluorescence, and ultrastructural study of malignant islet-cell tumors of the pancreas induced in hamsters by BK human papovavirus.

Histologic, immunofluorescence and ultrastructural studies were performed in 17 cases of pancreatic carcinomas induced by the BK virus in Syrian hamsters, a unique model of experimentally induced malignant islet cell tumors. The tumors were composed of small, poorly differentiated cells mostly arranged in a trabecular structure. By immunofluorescence all four islet cell types were found in the tumors, though with different frequency. Insulin cells were present in 16 cases, glucagon cells in 11, somatostatin cells in 7, PP cells in 6. Thirteen tumors contained more than one cell type. Insulin cells were the most frequent cell type in 13 cases, and glucagon cells predominated in 1 case. Insulin-containing cells usually occupied a central position within tumor-cell aggregates, while the other cell types were mostly located in a peripheral position, a distribution reminiscent of that seen in normal islets. Gastrin and calcitonin immunoreactivities were not observed. Immunoreactive cells were more abundant in tumors with trabecular structure. Argyrophil cells revealed by the Grimelius method often exceeded the cumulative number of immunoreactive cells in the same tumor, which suggests that there were additional cell types. Multiple cell types were also found in liver metastases. Ultrastructurally most neoplastic cells were poorly granulated. The occurrence of many damaged cells suggests hormone leakage, which may account, at least in part, for the deregulated hormone release from the tumors.

Adenoma, Islet Cell↗
PubMed1985

Restricted replication of BK virus in human lymphocytes.

Human lymphocytes from either peripheral blood or continuous cultures (P3HR-1 cells) are able to support the replication of prototype polyomavirus BK (BKV) as well as its related strain BO15 virus (BO15V). Instead, human monocytes from peripheral blood, although able to bind and egulf BKV virions, do not express virus-specific antigens within a 50 day observation period. In the light of these results, a probable role is suggested for human mononuclear blood cells in the mechanism of natural infection by polyomaviruses.

Antigens, Viral↗
PubMed1984

BK virus-plasmid expression vector that persists episomally in human cells and shuttles into Escherichia coli.

We describe a novel expression vector, pBK TK-1, that persists episomally in human cells that can be shuttled into bacteria. This vector includes sequences from BK virus (BKV), the thymidine kinase (TK) gene of herpes simplex virus type 1, and plasmid pML-1. TK+-transformed HeLa and 143 B cells contained predominantly full-length episomes. There were typically 20 to 40 (HeLa) and 75 to 120 143 B vector copies per cell, although some 143 B transformants contained hundreds. Low-molecular-weight DNA from TK+-transformed cells introduced into Escherichia coli were recovered as plasmids that were indistinguishable from the input vector. Removal of selective pressure had no apparent effect upon the episomal status of pBK TK-1 molecules in TK+-transformed cells. BKV T antigen may play a role in episomal replication of pBK TK-1 since this viral protein was expressed in TK+ transformants and since a plasmid that contained only the BKV origin of replication was highly amplified in BKV-transformed human cells that synthesize BKV T antigen.

BK Virus↗
PubMed1983

Episomal DNA of a BK virus variant in a human insulinoma.

BK virus (BKV) DNA was detected by blot hybridization in a human adenoma of pancreatic islets from patient I.R. BKV DNA was free, and no evidence was found of viral sequences integrated into cellular DNA. Virus was rescued by transfection of human embryonic fibroblasts with tumor DNA. The DNA from rescued virus (BKV-IR) was different from wild-type BKV DNA by restriction endonuclease mapping. The genome of BKV-IR is 235 base pairs (bp) shorter than the genome of wild-type BKV. This alteration originates from a deletion of approximately 300 bp involving HindIII fragments B and D, and an insertion of 70 bp in the region of HindIII fragment C. Transformation of hamster kidney cells was induced by total tumor DNA as well as by BKV-IR and BKV-IR DNA. No antibodies to BKV tumor (T) antigen were detected in the patient's serum by immunofluorescence. The significance of episomal BKV DNA in a human tumor is discussed.

Adenoma, Islet Cell↗
PubMed1983

BK virus-induced tumors in hamsters: a morphological, histochemical and ultrastructural study.

Macroscopic morphology, histology and ultrastructure of BK virus (BKV)-induced hamster and mouse tumors were investigated. Groups of animals were immunosuppressed to study the relationship between immune system and BKV oncogenesis. Ependymomas had the highest incidence, followed by tumors of pancreatic islets, osteosarcomas, lymphomas and sarcomas, sometimes associated in the same animal. All the tumors were found to be BKV specific. Ependymomas showed the shortest latency, infiltrated surrounding tissues but did not metastasize. Pseudo-rosettes were common and basal bodies were observed. Atypia and necrosis were more often present in immunosuppressed animals both for the ependymomas and for the other oncotypes. Pancreatic insulomas were frequently multinodular, possibly because of multifocal origin and metastasized to the liver. Hormone secretory granules were often found on electron microscopy. Osteosarcomas metastasized to lungs and peritoneum and showed the presence of osteoid, chondroblastoid and mixoid areas. Characteristic giant cells were present. Immunosuppression did not enhance tumor incidence and did not influence the latency period. However, neoplastic growth appeared to be more rapid and with more aggressive behavior in immunodepressed animals. These findings suggest an influence of the immune system in tumor development, whereas the virus oncogenic process seems unaffected.

Animals↗
PubMed1983

Formation of oligomeric free BK virus DNA is required for tandem integration of viral genomes into cellular DNA.

Mouse kidney cells have been transformed by linear BK virus (BKV) DNA with cohesive ends. These BKV genomes can circularize and subsequently replicate or physically join end to end yielding oligomeric viral DNA molecules. Blot hybridization analysis of transformed cells showed the presence of BKV DNA both in free circular forms and integrated into cellular DNA in a tandem head-to-tail array of full-length viral genomes. Formation of oligomers either by replication via previous circularization or by end to end joining is hindered after elimination of cohesive termini by digestion with the single-strand-specific nuclease S1. After treatment of linear BKV DNA with nuclease S1 only integrations of single viral genomes were observed in transformed cells; tandem insertions and free viral DNA were absent. These results support the hypothesis that formation of tandems of free viral DNA is a necessary prerequisite for tandem integration of viral genomes.

Animals↗
PubMed1982

Oncogenity of BK virus for immunosuppressed hamsters.

Tumors were induced by BK virus (BKV) inoculated intravenously in 3-week-old Syrian golden hamsters immunosuppressed with anti-lymphocyte serum or methylprednisolone acetate alone or in association with gamma-radiation (60Co). The induced neoplasms were ependymoma, carcinoma of pancreatic islets, lymphoma, osteosarcoma, undifferentiated sarcoma, kidney and renal pelvis carcinoma, pheochromocytoma and hemangiosarcoma. High levels of insulin and glucagon and altered concentrations of glucose were detected in blood of animals with tumors of pancreatic islets. No antibodies to BKV tumor antigen (TAg) and low levels of hemagglutination-inhibition antibodies to BKV viral coat protein Ag were detected in hamster sera. BKV TAg was found in tumors by complement fixation. Blot hybridization analysis of tumor DNA showed the presence of both free and integrated BKV genomes in tumor cells. BKV DNA inoculated intravenously and subcutaneously in immunosuppressed or immunocompetent hamsters was not oncogenic, whereas it was weakly oncogenic when inoculated intracerebrally.

Animals↗