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S Scherneck

Publications and source records attributed to S Scherneck.

At least 55 records · Page 3Linked to original sources
PubMed1996

In vivo replication of hamster polyomavirus DNA displays lymphotropism in hamsters susceptible to lymphoma induction.

Using the whole body section hybridization technique, we monitored the organ- and age-specific pattern of replication of hamster polyomavirus (HaPV) DNA in a colony of Syrian hamsters, which are susceptible to lymphoma induction. Three phases of viral infection and replication could be distinguished: first, a phase of acute infection characterized by high levels of replication of HaPV DNA in the haemopoietic organs and the liver. This culminated 5 to 7 days post-infection (p.i.); second, at 10 days p.i., a phase of viral clearance became evident; and finally, a third phase reflected both the restriction of HaPV replication in adult hamsters and the accumulation of HaPV DNA at sites of tumour development. A remarkable conformity was observed between the tissue specificity of viral replication and the induced tumour profile: high levels of replication of HaPV DNA were restricted to cells of the haemopoietic system and lymphoid tumours were induced. As shown by in situ hybridization, the viral infection in non-haemopoietic organs was due to the dissemination of HaPV-infected blood cells.

Animals↗
PubMed1995

Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes.

A number of candidate tumor suppressor genes located on the human chromosome 17 are thought to have a role to play in the development of breast cancer. In addition to the p53 gene on 17p13.1 and the BRCA1 gene mapped to 17q12-21, other chromosomal regions for tumor suppressor genes have been suggested to exist on 17p13.3 and both the central and the distal parts of 17q, although definitive functional proof of their involvement in breast cancer tumorigenesis is still lacking. In this report we show that microcell transfer of a human chromosome 17 into wild-type p53 breast cancer cells CAL51 results in loss of tumorigenicity and anchorage-independent growth, changes in cell morphology and a reduction of cell growth rates of the neo-selected microcell hybrids. In the hybrid cells, which express the p53 wild-type protein, only the p- and the distal parts of the q arm of donor chromosome 17 are transferred. Thus, our results provide functional evidence for the presence of one or more tumor suppressor gene(s) on chromosome 17, which are distinct from the p53 and the BRCA1 genes.

Animals↗
PubMed1995

TP53 mutations and breast cancer prognosis: particularly poor survival rates for cases with mutations in the zinc-binding domains.

Acquired mutations in TP53 as well as immunohistochemically detectable protein expression have been implicated as prognostic factors for breast cancer. We have evaluated the relationship between mutations detected in 119 breast tumours and various clinicohistopathological indices, stratifying the mutations according to the functional domains as defined by the recent elucidation of the crystal structure of the protein. Patients with missense mutations located in regions encoding parts of the protein involved in zinc-binding had significantly decreased disease-free and overall survival relative to patients whose tumours had mutations in other domains. These results indicate that these biochemically defined domains also have biological relevance in terms of breast cancer disease course, and suggest that some mutations in TP53, more than others, can contribute to the development of clinically more aggressive and perhaps treatment resistant breast tumours. When confirmed, this will be of potential importance in predicting the clinical behaviour of breast cancer and its responsiveness to therapy.

Adult↗
PubMed1993

Mutations within the hamster polyomavirus large T antigen domain involved in pRb binding impair virus productive cycle and immortalization capacity.

Hamster polyomavirus (HaPV) causes lymphoma and leukemia when injected into newborn Syrian hamsters and achieves full transformation of rodent fibroblasts in vitro. It offers a comprehensive model to study at a molecular level the contributions of the viral oncogenes to neoplastic transformation in vitro and in the animal. We have investigated the ability of HaPV large T antigen to form a complex with the product of the retinoblastoma gene (pRb) in vitro. In this report, we demonstrate that HaPV large T antigen can indeed complex the pRb polypeptide. In order to investigate to what extent this interaction might contribute to tumor induction by the virus, we have introduced two different point mutations within the putative pRb-binding sequence of large T antigen, and as a preliminary to in vivo experiments we have studied their effects in vitro on some biological activities relevant to tumor induction. We show that the substitution (Glu-134-->Lys) obliterates pRb binding, suggesting that Glu-134 participates in the interaction between pRb and large T antigen, whereas the substitution (Glu-135-->Lys) has no effect. The Lys-134 mutation is strongly deleterious to the immortalization capacity of the viral genome, whereas the Lys-135 mutation has no effect. Neither of the two mutations affects the capacity of the viral genome to induce foci formation in the rat established cell line F111. These results indicate that the interaction between large T and pRb is required in the immortalization process but irrelevant to transformation. Both mutants show at least partial impairment of replication and productive cycle.

Amino Acid Sequence↗
PubMed1993

Linkage analysis in German breast cancer families with early onset of the disease, using highly polymorphic markers from the chromosome 17q11-q24 region.

Linkage analysis in German breast cancer families with early onset of the disease by using six markers on chromosome 17q11-q24 has been carried out. In the region between markers D17S250 and GH, three markers showed positive LOD scores at an estimated distance of zero. Evidence for linkage is greatest for D17S250, with a LOD score of 2.42.

Adult↗
PubMed1991

Identification and characterization of the hamster polyomavirus middle T antigen.

Hamster polyomavirus (HaPV) is associated with lymphoid and hair follicle tumors in Syrian hamsters. The early region of HaPV has the potential to encode three polypeptides (which are related to the mouse polyomavirus early proteins) and can transform fibroblasts in vitro. We identified the HaPV middle T antigen (HamT) as a 45-kDa protein. Like its murine counterpart, HamT was associated with serine/threonine phosphatase, phosphatidylinositol-3 kinase, and protein tyrosine kinase activities. However, whereas mouse middle T antigen associates predominantly with pp60c-src and pp62c-yes, HamT was associated with a different tyrosine kinase, p59fyn. The ability of HaPV to cause lymphoid tumors may therefore reside in its ability to associate with p59fyn, a potentially important tyrosine kinase in lymphocytes.

Amino Acid Sequence↗
PubMed1991

Comparison of different in situ hybridization techniques for the detection of human papillomavirus DNA in cervical smears.

Different hybridization methods were used for detection of human papillomavirus (HPV) DNA in cervical smears. The results obtained by filter in situ hybridization (FISH) are consistent with most of the reports recently published. To overcome the unsatisfactory limitations of this method, especially the difficulties to distinguish clearly between positive and negative signals, we developed an in situ hybridization protocol using a cytospin and 35S-labelled as well as biotinylated DNA-probes. For direct comparison of different methods, the samples were obtained from two groups of patients. One group were women with reiterated Papanicolaou smears III, IV; the other were women with reiterated Pap III, IV and additional histological scoring. In all cases but one, the different methods used have shown the same results. In one case the hybridization on slides using 35S-labelled as well as biotinylated probes gave a negative result, whereas the FISH method using a 32P-labelled probe allowed to detect of HPV 16 and 18 DNA only when more than 1 x 10(6) cells were present per filter. Our data demonstrate that in situ hybridization on slides is a specific and sensitive technique, which enables a clear distinction between positive and negative results using a small number of cells and which, especially with biotinylated probes, is suitable for application in routine work.

Biotin↗
PubMed1990

The hamster polyomavirus--a brief review of recent knowledge.

The hamster polyomavirus was first isolated by Graffi et al. in Berlin-Buch from skin epithelioma arising spontaneously in the Buch Syrian hamster colony. Virus particles are assembled in the nuclei of keratinized cell layer. The genome organization is identical to the murine polyomavirus genetic map including, in particular, the existence of a coding capacity for an early gene product analogous to the middle T antigen. The virus and the cloned DNA can immortalize primary cells and transform established cell lines from rodent origin. The HaPV can also induce lymphoma and leukemia after inoculation into newborn animals from a Potsdam Syrian hamster colony geographically separated from the colony affected by the spontaneous epitheliomas. The tumor incidence is high (30-80%), the latency short (4-8 weeks). The lymphomas are virus free but contain large amounts of nonrandomly deleted viral genomes. Transgenic mice produced by microinjection of HaPV DNA into the pronucleus of fertilized eggs of Gat: NMRI mice develop both, epitheliomas and lymphomas. The mice tumors contain extrachromosomal viral DNA. A search for a cellular host fully permissive for HaPV productive cycle in vitro lead to the conclusion that the hamster cells represent the most permissive context for the HaPV genome replication; however, in only one cell line the virus can be propagated by successive productive cycles leading to the establishment of a persistent infection.

Animals↗
PubMed1988

Analysis of hamster lymphomas for the presence of hamster papovavirus DNA.

The hamster papovavirus (HaPV) is a polyomavirus isolated from skin epitheliomas arising spontaneously in young Syrian hamsters. It can induce lymphomas and leukaemias in newborn hamsters. Although no virus particles are detectable by electron microscopy, high amounts of monomeric and oligomeric forms of extrachromosomal HaPV DNA molecules are found in the lymphoma cells. These molecules display deletions of about 300 nucleotides in length. Their role in the lymphoma induction is discussed.

Animals↗
PubMed1987

Induction of lymphomas by the hamster papovavirus correlates with massive replication of nonrandomly deleted extrachromosomal viral genomes.

The hamster papovavirus isolated from skin epithelioma can induce lymphomas and leukemias after subcutaneous inoculation into newborn hamsters. The lymphoma cells are virus free but contain large amounts of extrachromosomal hamster papovavirus DNA. We have cloned and partly sequenced some of these DNA molecules from independent tumors. These genomes displayed overlapping deletions consistently sharing a common end within the noncoding regulatory sequences; the other end was variable but always extended into the sequence coding for the N-terminal part of the viral capsid VP2. This unique in vivo interaction between a polyomavirus and its cellular host, the genesis of these variant molecules, and their role in the lymphoma formation are discussed.

Animals↗
PubMed1987

A novel system for studying in vivo effects of tumor promoters on DNA tumor viruses.

An animal system is described that allows the analysis of the interaction of persisting hamster papovavirus (HaPV) genomes with the tumor-promoting phorbol ester TPA. In a colony of HaPV-bearing Syrian golden hamsters, extrachromosomal HaPV genomes were detected by Southern blot hybridization in DNA isolated from skin biopsies. Chronic topical treatment of hamsters with TPA resulted in a dramatic increase of viral DNA in skin cells at the site of TPA application. After finishing the TPA treatment, the amount of extrachromosomal viral DNA declined but was still enhanced more than three months thereafter. This model offers the possibility of investigating, at the molecular level, the initiating role of virus in tumorigenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

The hamster papovavirus: evolutionary relationships with other polyomaviruses.

The hamster papovavirus (HaPV) is a polyoma virus with a restricted tumor spectrum. It is actively replicated in hair follicle tumors arising spontaneously in young Syrian hamsters. It can also induce lymphomas and leukemias in newborn hamsters. The complete nucleotide sequence of a cloned HaPV has been established recently. This report presents a comparison of this sequence with other polyomavirus genomes (polyoma, SV40, BKV, LPV) by matrix dot analysis and electron microscopy heteroduplex mapping. The results demonstrate a close relationship between the HaPV and the murine polyoma virus and designate the LPV as the closest relative among the primate polyomaviruses.

Animals↗
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↗
PubMed1986

Studies on the SV40-like papovavirus SV40-GBM. III. Propagation at low multiplicities of infection in various human cell lines.

At low multiplicity several human cell lines supported the lytic infection with SV40-GBM better than that with the wild type SV40. The efficiency of viral DNA replication differed in the cell lines used suggesting that specific host cell factors may determine the rate of viral DNA synthesis. Furthermore, the emergence of different DNA defects during propagation of the virus indicates that host cell factors in question might also influence the composition of the viral DNA population.

Cell Line↗
PubMed1986

Characterization of the DNA of the hamster papovavirus: IV. Transcription mapping of calf-thymus DNA polymerase II.

Nascent RNA, synthesized by calf thymus RNA polymerase II on restriction endonuclease BamHI linearized hamster papovavirus (HaPV) DNA, was rehybridized to the template strand under conditions allowing transcription R-loop formation. Hybrids, visualized by electron microscopy, were plotted and mapped according to the physical map of HaPV. Two predominant regions of transcription could be localized at 0.10--0.40 and 0.50--0.82 m.u., respectively. For the start sites of transcription at map positions 0.67 and 0.75, respectively, on the HaPV genome a transcription in opposite direction were estimated. This genome region harbours the putative origin of replication of HaPV DNA. These results suggest a distinct relatedness of HaPV to the polyomavirus group.

Animals↗
PubMed1986

Characterization of the DNA of the hamster papovavirus. III. Mapping of inverted repeated DNA sequences within the viral genome.

Sequences with 2-fold axis of symmetry (inverted repeated sequences) have been detected and mapped on the hamster papovavirus (HaPV) genome by their ability to form secondary structures like hairpins or stem-loops on single-stranded HaPV DNA. DNA regions with secondary structure were visualized by electron microscopy and mapped according to the physical map of HaPV. Eleven positions containing inverted repeats could be determined. The nucleotide sequence within all of these inverted repeats may be related since these regions can crosshybridize with each other. The possible functions of these sequences within the HaPV genome are discussed with respect to conditions found for genomes like those from SV40 and polyoma virus to get first indications for the localization of DNA regions representing the origin and termination of replication of HaPV DNA.

Animals↗
PubMed1985

A new member of the polyomavirus family: the hamster papovavirus. Complete nucleotide sequence and transformation properties.

The hamster papovavirus (HapV) is associated with multiple skin epitheliomas of the Syrian hamster. We have sequenced its genome. It is a double-stranded circular DNA of 5366 bp. The hypothetical genomic organization deduced from this nucleotide sequence is clearly of the polyoma type with the two strands coding in the opposite directions from a noncoding region that shows some of the features of a replication origin and a transcription control region. The amino acid sequences predicted from the open reading frames show an average of 50% homology with polyoma-coded polypeptides. The HapV is, after polyoma, the second example of a papovavirus coding for a middle T antigen. The cloned DNA can immortalize primary rat embryo cells and transform an established rat cell line. The viral DNA is stably integrated into the host genome.

Animals↗