Abstract
Squamous (epidermoid) metaplasia is a common abnormality of development and differentiation, in which various epithelia are replaced by cells resembling those of the epidermis. The metaplastic cells differentiate into flattened cells that frequently form keratotic flakes and whorls. The cells may regress, remain benignly squamous, or progress to epidermoid carcinoma1. Squamous metaplasias have previously been brought about by mechanical injury2, vitamin A deficiency3,4 and chemical carcinogens5–7. In search of the physiological mediators of abnormal development and differentiation in oncogenesis, we have now discovered that the combination of dibutyryl cyclic AMP, prostaglandins (PGs) E1, E2 and B1, and papaverine (Pap) induces squamous metaplasia with keratin production in the epithelium of cultured mammary glands. The three inducers may act synergistically to elevate the level of intracellular cyclic adenine nucleotide. Removal of these inducers causes the regression of the metaplastic cells. Retinoid does not block the induction of this squamous metaplasia, even though retinoid has previously prevented and reversed the squamous metaplasias caused by vitamin A deficiency or chemical carcinogens in other organs4,8. The findings suggest that cyclic adenine nucleotide and the PGs may mediate the squamous metaplasias present in many abnormal, transformed and malignant tissues, and possibly also the normal development and differentiation of epithelia into keratin-producing, stratified squamous cells, as in skin.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Anderson, W. A. D. & Kissane, J.M. in Pathology Vol. 1, 7th edn, 84–85 (Mosby, St. Louis, 1977).
McDowell, E. M., Becci, P. J., Schurch, W. & Trump, B. F. J. natn. Cancer Inst. 62, 995–1008 (1979).
Wolbach, S. B. & Howe, P. R. J. exp. Med. 42, 753–777 (1925).
Marchok, A. C., Cone, M. V. & Nettesheim, P. Lab. Invest. 33, 451–460 (1975).
Lasnitski, I. Br. J. Cancer 5, 345–352 (1951).
Harris, C. C. et al. J. natn. Cancer Inst. 48, 743–761 (1972).
Tonelli, Q.J., Custer, R.P. & Sorof, S. Cancer Res. 39, 1784–1792 (1979).
Sporn, M. B., Dunlop, N. M., Newton, D. L. & Smith, J. M. Fedn Proc. 35, 1332–1338 (1976).
Ichinose, R. R. & Nandi, S. J. Endocr. 35, 331–340 (1966).
Wood, B. G., Washburn, L. L., Mukherjee, A. S. & Banerjee, M. R. J. Endocr. 65, 1–6 (1975).
Terry, P. M., Ball, E. M., Ganguly, R. & Banerjee, M. R. J. immun. Meth. 9, 123–134 (1975).
Tonelli, Q. J. & Sorof, S. Nature 285, 250–252 (1980).
Banerjee, M. R., Wood, B. G. & Washburn, L. L. J. natn. Cancer Inst. 53, 1387–1393 (1974).
Telang, N.T., Banerjee, M. R., Iyer, A. P. & Kundu, A. B. Proc. natn. Acad. Sci. U.S.A. 76, 5886–5890 (1979).
Dickens, M. S., Custer, R. P. & Sorof, S. Proc. natn. Acad. Sci. U.S.A. 76, 5891–5895 (1979).
Kundu, A. B., Telang, N. T. & Banerjee, M. R. J. natn. Cancer Inst. 61, 465–469 (1978).
Dickens, M. S. & Sorof, S. Nature 285, 581–584 (1980).
Prasad, K. N. & Kumar, S. in Control of Proliferation in Animal Cells (eds Clarkson, B. & Baserga, R.) 581 (Cold Spring Harbor Laboratory, New York, 1974).
Samuelsson, B., Granström, E., Green, K., Hamberg, M. & Hammarström, S. A. Rev. Biochem. 44, 669–695 (1975).
Samuelsson, B. et al. A. Rev. Biochem. 47, 997–1029 (1978).
Perry, J. W. & Oka, T. Proc. natn. Acad. Sci. U.S.A. 77, 2093–2097 (1980).
Pasternack, J. G. & Wirth, J. E. Am. J. Path. 12, 423–437 (1936).
Deringer, M.K. J. natn. Cancer Inst. 22, 995–1002 (1959).
Huvos, A. G., Lucas, J. C. & Foote, F. W. N. Y. St. J. Med. 73, 1078–1082 (1973).
Medina, D. J. natn. Cancer Inst. 53, 213–221 (1974).
Hassan, M. O. & Olaizola, M. Y. Archs Path. Lab. Med. 103, 624–630 (1979).
Taylor-Papadimitriou, J., Purkis, P. & Fentiman, I.S. J. cell. Physiol. 102, 317–321 (1980).
Green, H. Cell 15, 801–811 (1978).
Friedman, D. L. Physiol. Rev. 56, 652–708 (1976).
Johnson, G. S., Friedman, R. M. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 68, 425–429 (1971).
Hsie, A. W. & Puck, T. T. Proc. natn. Acad. Sci. U.S.A. 68, 358–361 (1971).
Sheppard, J.R. Proc. natn. Acad. Sci. U.S.A. 68, 1316–1320 (1971).
Aw, E. J., Holt, P. G. & Simons, P. J. Expl Cell Res. 83, 436–438 (1973).
Johnson, G. S. & Pastan, I. Nature new Biol. 237, 269–270 (1972).
Chopra, D. Br. J. Derm. 96, 255–262 (1977).
Sun, T.-T., Shih, C. & Green, H. Proc. natn. Acad. Sci. U.S.A. 76, 2813–2817 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schaefer, F., Philip Custer, R. & Sorof, S. Induction of abnormal development and differentiation in cultured mammary glands by cyclic adenine nucleotide and prostaglandins. Nature 286, 807–810 (1980). https://doi.org/10.1038/286807a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/286807a0
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.