Effect of oncogenic virus on muscle differentiation.

Holtzer, H.; Biehl, J.; Yeoh, George; Meganathan, R; Kaji, Akira

doi:10.1073/pnas.72.10.4051

Cited by 141 publications

(71 citation statements)

References 27 publications

(31 reference statements)

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“…It also agrees with the lack of morphological changes in late-infected myotubes (Fig. 2d, e and f ) because the expression of the v-src protein would have caused a morphological deterioration in myotubes (Holtzer et al, 1975;pathway IV in Fig. 1 of Tanaka et al, 1992).…”

Section: Detection Of Viral Proteins In Late-infected Myotubes By Immsupporting

confidence: 85%

“…In this experiment, some of the early-infected myotube cultures had been shifted down to the permissive temperature (37 °C) prior to labelling. This procedure induced breakage of myotubes, as has been observed previously (Holtzer et al, 1975;Kobayashi & Kaji, 1978), but the profile of none of the radioactive viral proteins was significantly influenced by this temperature shift.…”

Section: Normal Amounts Of Radioactive V-sre and Env Proteins In Earlsupporting

confidence: 78%

“…Thus these studies indicated that the gag and pol proteins, but not the v-src protein, were produced normally in late-infected myotubes. We considered the possibility that the deleterious effect of the v-src protein in late-infected myotubes (Holtzer et al, 1975) …”

Section: Detection Of Viral Proteins In Late-infected Myotubes By Immmentioning

confidence: 99%

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Infection of terminally differentiated myotubes with Rous sarcoma virus: reduced synthesis of env and v-src proteins

Hsia¹,

Hara

Izutani

et al. 1992

Journal of General Virology

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We studied Rous sarcoma virus (RSV) protein synthesis in RSV-infected, terminally differentiated chicken myotubes ('late-infected' myotubes), in which no viral DNA integration takes place but all three viral mRNAs (38S, 28S and 21 S) are transcribed normally. With the use of specific anti-RSV protein antisera, we found that only the viral gag and pol proteins were synthesized at levels similar to those synthesized in RSVtransformed fibroblasts; the synthesis of env and v-src proteins was significantly reduced in these infected myotubes. We concluded that the viral RNA transcribed from the unintegrated RSV DNA was functional but that genes at the 3' end of the RSV genome were translated at a lower level. By contrast, when mononucleated replicating chicken myoblasts were infected with a mutant (tsNY68) carrying a temperature-sensitive v-src gene and maintained at the nonpermissive temperature for this gene, they developed into myotubes with viral DNA integrated in their chromosomal DNA. These 'early-infected' myotubes expressed all four viral genes (gag, pol, env and v-src) at a level similar to that in infected fibroblasts. This result ruled out the possible presence of specific factor(s) in myotubes that preferentially inhibit the 3' genes of RSV, and suggested other translational control(s) of viral gene expression in late-infected myotubes.

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Section: Detection Of Viral Proteins In Late-infected Myotubes By Immsupporting

confidence: 85%

Section: Normal Amounts Of Radioactive V-sre and Env Proteins In Earlsupporting

confidence: 78%

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Infection of terminally differentiated myotubes with Rous sarcoma virus: reduced synthesis of env and v-src proteins

Hsia¹,

Hara

Izutani

et al. 1992

Journal of General Virology

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“…In addition to promoting tumor formation, anchorage-independent growth, and cellular immortalization, expression of transforming oncogenes inhibits cellular differentiation in several different cell lineages. In muscle cells, expression of oncogenic tyrosine kinases (v-src and v-fps), growth factor receptors (v-erbB), nuclear oncogene products (v-myc, c-myc, v-erbA, and E1A), and the activated forms of signal-transducing G proteins (H-ras and N-ras) can inhibit terminal differentiation to various extents (5,7,10,14,30,31,37,45). We previously demonstrated that ras and fos prevent myogenesis by inhibiting expression of MyoD (19).…”

Section: Discussionmentioning

confidence: 99%

Amplification of MDM2 Inhibits MyoD-Mediated Myogenesis

Fiddler

Smith

Tapscott

et al. 1996

Molecular and Cellular Biology

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One obvious phenotype of tumor cells is the lack of terminal differentiation. We previously classified rhabdomyosarcoma cell lines as having either a recessive or a dominant nondifferentiating phenotype. To study the genetic basis of the dominant nondifferentiating phenotype, we utilized microcell fusion to transfer chromosomes from rhabdomyosarcoma cells into C2C12 myoblasts. Transfer of a derivative chromosome 14 inhibits differentiation. The derivative chromosome 14 contains a DNA amplification. MDM2 is amplified and overexpressed in these nondifferentiating hybrids and in the parental rhabdomyosarcoma. Forced expression of MDM2 inhibits MyoD-dependent transcription. Expression of antisense MDM2 restores MyoD-dependent transcriptional activity. We conclude that amplification and overexpression of MDM2 inhibit MyoD function, resulting in a dominant nondifferentiating phenotype.Rhabdomyosarcomas are one of the most common solid tumors of childhood. Sarcomas have traditionally been classified as rhabdomyosarcomas on the basis of morphology and the expression of muscle structural genes, such as that for the myosin heavy chain (MHC) or desmin. Expression of MyoD has been shown to be the most sensitive marker for classifying sarcomas as rhabdomyosarcomas (4, 38). Rhabdomyosarcomas are grouped by histologic and cytogenetic criteria as either embryonal or alveolar rhabdomyosarcomas: a balanced translocation between chromosomes 2 and 13, t(2;13)(q35;q14), is associated with alveolar rhabdomyosarcomas (1). The PAX3 gene has been shown to be fused to a member of the forkhead gene family in the t(2;13) translocation (1, 39). Loss of heterozygosity on the short arm of chromosome 11 encompassing 11p15.5 is associated not only with embryonal rhabdomyosarcomas (38) but also with a number of other solid tumors (26), suggesting the location of a tumor suppressor gene(s) for multiple tumor types in this region.Recently, we have begun an analysis of five rhabdomyosarcoma cell lines (RD, Rh18, Rh28, Rh30, and RhJT) for expression and function of the MyoD family (42). We showed that even though MyoD is expressed in rhabdomyosarcoma cells, it is nonfunctional in inducing differentiation. Heterokaryon formation between 10T1/2 cells and RD, Rh28, Rh30, and RhJT cells results in differentiation of the heterokaryons into muscle and restoration of transcriptional activation by MyoD, indicating that these tumor lines display a recessive nondifferentiating phenotype. In contrast, heterokaryon formation with the rhabdomyosarcoma Rh18 and 10T1/2 cells did not result in myogenesis, suggesting that Rh18 cells display a dominant nondifferentiating phenotype.In this paper, we show that transfer of a derivative chromosome 14 from Rh18 cells into the differentiation-competent myoblast cell line C2C12 inhibits muscle differentiation and the ability of MyoD to function as a transcription factor. The derivative chromosome 14 contains a region of amplified DNA originating from chromosome 12 and contains a number of genes often amplified in sarcomas, ...

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“…In contrast, a shift in the proliferative state of myoblasts, from a replicating population to a quiescent one, appears to be obligatory for myogenesis; the continued capacity to replicate is incompatible with myogenesis (7,11,15,21,23,24) and experimental manipulations which initiate DNA synthesis in differentiated cells reverse the myogenic phenotype (11,22,24). Thus the cessation and maintenance of suppression of DNA synthesis is a stringent requirement for skeletal muscle to develop.…”

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confidence: 99%

DNA Replication and differentiation in rat myoblasts studied with monoclonal antibodies against 5‐bromodeoxyuridine, actin, and α2‐macroglobulin

Kaufman

Robert‐Nicoud

1985

Cytometry

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During the differentiation of skeletal muscle, mononucleate myoblasts proliferate, then stop replicating, spontaneously fuse, and express a large number of genes which encode the muscle phenotype. We have used monoclonal antibodies specific for 5-bromodeoxyuridine, myoactin, and equine a2-macroglobulin to follow and establish the sequence of events that surround the transition from a replicating to a differentiating population. Triple-label immunofluorescence microscopy was used to visualize the changes in DNA synthesis, formation of myoactin fibers, and the cessation of endocytosis of a2-macroglobulin that accompany myogenesis. Our results indicate that myoblasts cease actively endocytosing a2-macroglobulin after stopping DNA synthesis but prior to fusion. Formation of myoactin fibers rarely occurs in mononucleate myoblasts and only in post-mitotic cells, but they are common in multinucleate myotubes. We suggest that the regulation of DNA synthesis is critical to normal myogenesis and that detection of incorporated BrdUrd by immunofluorescence, in conjunction with other antibodies and nucleic acid probes, is a convenient method with which to study and sequence the molecular events in single cells as they relate to the transition in DNA synthesis that accompanies differeritialion.

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Effect of oncogenic virus on muscle differentiation.

Cited by 141 publications

References 27 publications

Infection of terminally differentiated myotubes with Rous sarcoma virus: reduced synthesis of env and v-src proteins

Infection of terminally differentiated myotubes with Rous sarcoma virus: reduced synthesis of env and v-src proteins

Amplification of MDM2 Inhibits MyoD-Mediated Myogenesis

DNA Replication and differentiation in rat myoblasts studied with monoclonal antibodies against 5‐bromodeoxyuridine, actin, and α2‐macroglobulin

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