Partial reversion of the transformed phenotype of murine sarcoma virus-transformed cells in the presence of interferon: A possible mechanism for the anti-tumour effect of interferon

Hicks, Nigel John; Morris, A. G.; Burke, D. C.

doi:10.1242/jcs.49.1.225

Cited by 41 publications

(2 citation statements)

References 18 publications

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“…laboratories (6,11), the mechanism by which IFN inhibits retrovirus release from infected cells is apparently different from that which inhibits lytic RNA viruses. A5 and A10 cells were treated with IFN, infected with MLV, and further incubated in the presence of IFN for 24 h. The amount of virus particles released was determined by monitoring reverse transcriptase activity in the culture medium.…”

Section: Resultsmentioning

confidence: 99%

“…Interferon (IFN) is known to induce a cell growth inhibitory effect, in addition to the antiviral state which arrests the replication of a wide range of DNA and RNA viruses (23,24). It is not clear, however, whether the cell growth inhibitory effect is directed preferentially against tumor growth (9, 23), although some reports have indicated that IFN induces the reversion of the transformed phenotype of murine sarcoma virus-transformed fibroblasts (11) and inhibits their proliferation (4).…”

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Isolation and Characterization of an Interferon-Resistant Cell Line Deficient in the Induction of (2′-5′)Oligoadenylate Synthetase Activity

Salzberg

Wreschner

Oberman

et al. 1983

Molecular and Cellular Biology

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To screen for cells with different sensitivities to interferon (IFN), NIH 3T3 mouse fibroblasts were subcloned and examined for their response to IFN treatment. Of 30 clones tested, 2 appeared to be relatively resistant to IFN, since the replication of both vesicular stomatitis virus and mengovirus was not inhibited, even in the presence of 1,000 U of IFN per ml. One resistant (A10) and one sensitive (A5) clone were further analyzed. In both clones, murine leukemia virus replication was equally inhibited by IFN, indicating the presence of functional receptors for IFN in the resistant clone. Using the (2'-5')oligoadenylate (2-5A) radiobinding assay, we could demonstrate that both clones contained the RNase L protein. Furthermore, this enzyme appears to be active, since a similar reduction in the rate of protein synthesis was evident after the introduction of exogenous 2-5A to the cells. We also analyzed the activity of another enzyme in the 2-5A pathway, namely, 2-5A synthetase. In the sensitive cells (A5), the induction of enzyme activity was proportional to the IFN concentration used, reaching a maximum of more than a 10-fold increase over the background of untreated cells. However, little if any induction over the basal activity was observed in the resistant cells (A10) when similar doses of IFN were used. It is thus probable that the lack of induction of 2-5A synthetase activity by IFN in A10 cells is at least partly responsible for their relative resistance to IFN treatment.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Isolation and Characterization of an Interferon-Resistant Cell Line Deficient in the Induction of (2′-5′)Oligoadenylate Synthetase Activity

Salzberg

Wreschner

Oberman

et al. 1983

Molecular and Cellular Biology

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The mechanism of interferon effect on cell transformation by murine sarcoma virus

Huleihel

Marvit

Aboud

1983

Intl Journal of Cancer

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Mouse interferon (IFN) was found to inhibit murine sarcoma virus (MSV)-induced neoplastic transformation of normal rat kidney (NRK) cells. This effect was observed upon examining the formation of foci of morphologically altered cells and colonies of anchorage-independent cells. IFN had no cytotoxic effect on MSV-transformed NRK cells, nor on their focus or colony-forming ability. It was therefore apparent that its inhibitory effect was directed against the viral role in cell transformation. In attempts to define the mechanism of this effect, we found that IFN delayed the initiation of the cytoplasmic viral DNA synthesis. However, the amount of this DNA eventually formed in IFN-treated cells was the same as in the control cells. Furthermore, the transport of this DNA to the nucleus was slower in IFN-treated cells, although all of it was finally transferred. However, while most of the viral DNA integrated into the genome of the control cells, very little integration occurred in IFN-treated cells. The unintegrated viral DNA of these cells was slowly degraded. Therefore, if the cells recovered from the antiviral effect of IFN when intact viral DNA molecules still existed in their nucleus, they could resume viral DNA integration and cell transformation. IFN was found to block viral DNA supercoiling. Since supercoiled viral DNA is considered to be a precursor to integrated provirus, it seems that the inhibition of both integration and cell transformation is due to this impaired coiling.

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Dissociation of proto‐oncogene induction from growth response in normal human fibroblasts

Yaar

Peacocke

Cohen

et al. 1990

Journal Cellular Physiology

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Proto-oncogenes are cellular homologues of viral oncogenes that are known to be associated with regulation of growth and differentiation. The c-myc and c-fos proto-oncogenes have been extensively studied by using established cell lines but to a lesser extent by using normal cells. Using physiologic growth modulators, we have shown that mitotic stimulation of normal human dermal fibroblasts is associated with induction of c-myc and c-fos, but that growth inhibition of these cells is not necessarily accompanied by their down-regulation. When treated with both serum and interferon-alpha during quiescence, fibroblasts were delayed in their progress into the S-phase of the cell cycle as compared to cells treated with serum alone and displayed substantial growth inhibition as measured by cell number at the end of 1 week. However, this growth inhibition was not preceded by down-regulation or delay in induction of c-myc and c-fos mRNA. The above studies suggest that in normal fibroblasts growth inhibition is not necessarily dependent on down-regulation of transcription of either c-myc or c-fos and that interferon may act to inhibit cell growth either through a post-transcriptional effect on cellular proto-oncogenes necessary for cell proliferation or through induction of other, as yet unrecognized gene(s) associated with growth arrest.

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Partial reversion of the transformed phenotype of murine sarcoma virus-transformed cells in the presence of interferon: A possible mechanism for the anti-tumour effect of interferon

Cited by 41 publications

References 18 publications

Isolation and Characterization of an Interferon-Resistant Cell Line Deficient in the Induction of (2′-5′)Oligoadenylate Synthetase Activity

Isolation and Characterization of an Interferon-Resistant Cell Line Deficient in the Induction of (2′-5′)Oligoadenylate Synthetase Activity

The mechanism of interferon effect on cell transformation by murine sarcoma virus

Dissociation of proto‐oncogene induction from growth response in normal human fibroblasts

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