Letter | Published:

Effect of a tumour promoter on myogenesis

Naturevolume 266pages538540 (1977) | Download Citation

Subjects

Abstract

EVIDENCE that viruses and chemical carcinogens alter the ongoing synthetic programme of cells has been presented1,2. Chondroblasts and melanoblasts transformed with a temperature-sensitive Rous sarcoma virus cease synthesising the chondroblast-unique sulphated proteoglycan and melanin, respectively3. Shifted to non-permissive temperature, these cells re-initiate the synthesis of the chondroblast-unique sulphated proteoglycan and melanin. Similar results have been obtained using chick myogenic cells4,5. Normal presumptive myoblasts undergo a limited number of replications, yielding postmitotic, mononucleated myoblasts. Postmitotic myoblasts initiate the synthesis of muscle-specific myosin heavy and light chains and fuse into myotubes6,7. In contrast, ts-viral transformed myogenic cells continue to replicate, do not initiate the synthesis of muscle-specific myosins and do not fuse. 24–48 h after shifting to non-permissive temperature, many transformed myogenic cells withdraw irreversibly from the cell cycle, initiate the synthesis of muscle-specific (unpublished data) myosins and fuse. Apparently when the transformation factor is expressed the cells do not withdraw from the cell cycle, and as a consequence of being forced to cycle, do not terminally differentiate. To probe the mechanisms that might be common to the generation of terminally differentiated cells from normal precursor cells, and to the generation of malignant cells from normal precursor cells, we studied the effects of phorbol-12-myristate-13-acetate (PMA) on myogenesis. Of the purified phorbol esters, PMA is the most potent as a tumour-promoting agent and as a mitogen8–12. We report here that PMA mimics some of the effects of the Rous sarcoma tumour agent on myogenesis.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Tooze, J. The Molecular Biology of Tumour Viruses (Cold Spring Harbor Press, 1973).

  2. 2

    Berenblum, I. in Frontier of Biology: Carcinogenesis as a Biological Problem (eds Neuberger, A. & Tatum, E.) 67–73 (North-Holland, Amsterdam, 1974).

  3. 3

    Roby, K., Boettiger, D., Pacifici, M. & Holtzer, H. Am. J. Anat. 147, 401–405 (1976).

  4. 4

    Fiszman, M. & Fuchs, P. Nature 254, 429–431 (1976).

  5. 5

    Holtzer, H., Biehl, J., Yeoh, G., Meganathan, R. & Kaji, A. Proc. natn. Acad. Sci. U.S.A. 72, 4051–4055 (1976).

  6. 6

    Holtzer, H., Strahs, K., Biehl, J., Somlyo, A. & Ishikawa, H. Science 188, 943–945 (1975).

  7. 7

    Chi, J., Fellini, S. & Holtzer, H. Proc. natn. Acad. Sci. U.S.A. 72, 4999–5003 (1976).

  8. 8

    Hecker, E. Cancer Res. 28, 2338–2349 (1968).

  9. 9

    Sivak, A. & van Duuren, D. Science 157, 1443–1444 (1967).

  10. 10

    Diamond, L., O'Brien, S., Donaldson, C. & Shimizu, Y. Int. J. Cancer. 13, 721–730 (1974).

  11. 11

    Wegler, M. & Weinstein, B. Nature 259, 232–233 (1976).

  12. 12

    O'Brien, T., Sisiman, R. & Boutwell, R. Cancer Res. 2426–2433 (1975).

  13. 13

    Bischoff, R. & Holtzer, H. J. Cell Biol. 41, 188–197 (1969).

  14. 14

    Adelstein, R., Conti, M., Johnson, G., Pastan, I. & Pollard, T. Proc. natn. Acad. Sci. U.S.A. 69, 3693–3697 (1972).

  15. 15

    Chi, J., Rubinstein, N. & Holtzer, H. J. Cell Biol. 67, 523–537 (1975).

  16. 16

    Holtzer, H., Croop, J., Dienstman, S., Ishikawa, H. & Somylo, A. Proc. natn. Acad. Sci. U.S.A. 72, 513–517 (1976).

  17. 17

    Paterson, B. & Strohman, R. Devl Biol. 29, 113–136 (1972).

  18. 18

    Dienstman, S. & Holtzer, H. in Cell Cycle and Cell Differentiation (eds Reinert, J. & Holtzer, H.) 1–18 (Springer-Verlag, Heidelberg, 1975).

  19. 19

    Holtzer, H. & Sanger, J. in Research in Muscle Development and in the Muscle Spindle (eds Banker, B., Pryzblski, X. & Victor, M.) 22–36 (Excerpta Medica, Amsterdam, 1972).

  20. 20

    Holtzer, H. et al. Q. Rev. Biophys. 8, 523–557 (1975).

  21. 21

    Nameroff, M. & Munar, E. Devl Biol. 49, 288–293 (1976).

  22. 22

    Holtzer, H., Abbott, J. & Lash, J. Anat. Rec. 131, 567 (1958).

  23. 23

    Okazaki, K. & Holtzer, H. J. Histochem. Cytochem. 13, 726–738 (1965).

  24. 24

    Burton, K. Biochemistry 62, 315–323 (1956).

  25. 25

    Fellini, S. & Holtzer, H. Differentiation 6, 71–74 (1976).

  26. 26

    Offer, G. in Cold Spring Harb. Symp. quant. Biol. 37, 87–93 (1973).

Download references

Author information

Affiliations

  1. Department of Anatomy, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104

    • ROBERT COHEN
    • , MAURIZIO PACIFICI
    • , NEIL RUBINSTEIN
    • , JUDY BIEHL
    •  & HOWARD HOLTZER

Authors

  1. Search for ROBERT COHEN in:

  2. Search for MAURIZIO PACIFICI in:

  3. Search for NEIL RUBINSTEIN in:

  4. Search for JUDY BIEHL in:

  5. Search for HOWARD HOLTZER in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/266538a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.