Biomedical subjects

S Pfeifer-Ohlsson

Publications and source records attributed to S Pfeifer-Ohlsson.

22 records · Page 2Linked to original sources

PubMed1985

Nucleotide sequence of two overlapping myc-related genes in avian carcinoma virus OK10 and their relation to the myc genes of other viruses and the cell.

Avian carcinoma virus OK10 has the genetic structure gag-delta pol-myc-delta env. It shares the transformation-specific myc sequence with three other avian carcinoma viruses (MC29, MH2, CMII) and also with a normal chicken gene proto-myc and the gag, pol, and env elements with non-transforming retroviruses. Unlike the other myc-containing viruses, which synthesize singular myc proteins, OK10 synthesizes two different myc-related proteins of 200 and 57 kDa. Here we have sequenced the myc region of an infectious OK10 provirus to investigate how OK10 synthesizes two different proteins from the same myc domain and to identify characteristic differences between the normal proto-myc gene and the myc-related viral transforming genes. It was found that the 1.6-kilobase myc domain of OK10 is colinear and coterminal with the myc domains of MC29, MH2, and the terminal two exons of proto-myc. It is preceded by the same splice acceptor as the myc sequence of MH2 and as the second proto-myc exon. From this and the known structure of retroviruses, it follows that the OK10 gene encoding the 57-kDa protein is discontinuous with a small 5' exon that includes six gag codons and a large 3' myc exon (delta gag-myc). This gene and the delta gag-myc gene of MH2 are isogenic. The proto-myc-derived intron preceding the myc domain of OK10 is in the same reading frame as the adjacent delta pol and myc domains and, hence, is part of the gag-delta pol-myc gene encoding the 200-kDa protein. Sequence comparisons with proto-myc and MC29 and MH2 indicate that there are no characteristic mutations that set apart the viral myc domains from proto-myc. It is concluded that transforming function of viral myc-related genes correlates with the lack of a viral equivalent of the first proto-myc exon(s) and conjugation of the viral myc domains with large or small retroviral genetic elements rather than with specific point mutations. Because OK10 and MH2 each contain two genes with potential transforming function (namely, delta gag-myc and gag-delta pol-myc or delta gag-mht, respectively), it remains to be determined whether the delta gag-myc genes have transforming function on their own or need helper genes. The possible helper requirement cannot be very specific because the two potential helper genes are very different.

Alpharetrovirus↗

PubMed1984

Spatial and temporal pattern of cellular myc oncogene expression in developing human placenta: implications for embryonic cell proliferation.

We have analyzed staged human placentas by Northern, dot blot, and in situ hybridization to human c-myc probes. Placental RNA exhibits a stage-specific appearance of a 2.4 kb transcript of the c-myc gene. The frequency of this transcript varies 20 to 30 fold over the course of placental development, showing a peak at 4-5 weeks after conception, where the myc transcripts comprise about 0.05% by weight of the total placental mRNA. A clear decline in placental c-myc transcription is seen before the end of the first trimester of pregnancy. In situ hybridization to 125I-labeled myc probes demonstrates an unequal spatial distribution of myc transcripts in placental with particularly high expression in the cytotrophoblastic shell of early placenta. Labeling of placental explants with 3H-thymidine, the localization of myc transcripts to cytotrophoblasts, and the temporal pattern of myc expression all support a strong correlation between myc transcript abundance and cytotrophoblast proliferation. We argue for a role for the c-myc gene in the proliferation of normal cells in this tissue.

Cell Division↗

PubMed1984

OK10-transformed cell lines: viral component generation and tumorigenicity.

Stable nonproducer (NP) cell lines transformed by the avian acute leukemia virus OK10 were established. All 13 studied NP quail cell lines released into the culture medium noninfectious, mostly reverse-transcriptase-negative particles containing the usual gag proteins. Infectious, transforming OK10 virus pseudotypes could be recovered by rescue with helper virus. p200, the putative transforming protein of OK10, was identified in in vitro translates of RNA from the noninfectious particles and in immunoprecipitates of cell extracts of the NP clones analyzed. Two NP clones, the reverse-transcriptase-negative B5 and -positive 9C cell lines, displayed striking differences in in vivo tumorigenicity. Although B5 induced no tumors in quails, 9C caused multiple tumors and cells derived from several tumors could be passaged in vitro. At no time during the in vivo passage or during more than 1 year of in vitro culture have the particles released by 9C cells acquired infectious properties. Possible reasons for the observed differences in tumorigenicity between the OK10 virus-transformed 9C and B5 NP cell lines are discussed.

Animals↗

PubMedDate not supplied

Temporal and spatial pattern of cellular myc oncogene expression during human placental development.

The human placental trophoblast component is of embryonic origin and is developmentally regulated; the tissue is highly proliferative and often described as pseudomalignant. Because cellular oncogenes have been implicated in normal cellular proliferation and differentiation processes, we have studied c-myc oncogene expression in relation to the progression of human placental development. The c-myc transcript shows a 20- to 30-fold variation over the course of placental development, with a peak at four to five weeks after conception. A clear decline in placental c-myc transcription is seen before the end of the first trimester of pregnancy. In situ hybridization to [125I]-labelled myc probes demonstrates an unequal distribution of myc transcripts in placenta, with particularly high expression in the cytotrophoblastic shell of the early placenta. The localization of myc transcripts to cytotrophoblast and the temporal pattern of myc expression support a strong correlation between myc transcript abundance and cytotrophoblastic proliferation. These findings are discussed in the light of a possible role for the c-myc gene in proliferation of normal cells.

Female↗