Effect of a phorbol ester on a transformation-sensitive surface protein of chick fibroblasts

Effect of a phorbol ester on a transformation-sensitive surface protein of chick fibroblasts

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ABSTRACT PMA (phorbol myristate acetate) is the most active of a class of compounds present in croton oil which act as tumour promoters1–3. While PMA possesses little car-cinogenicity in its own night, its repeated application to mouse skin causes tumour induction in animals treated up to several months previously with a single subthreshold dose of a carcinogen. If the order of treatments is reversed, that is, if PMA treatment precedes that with the carcinogen, then no tumours are induced. Studies both with mouse skin and with cells in tissue culture indicate substantial effects of PMA on cell behaviour and biochemistry. Many of these effects such as alteration of phospholipid synthesis4 or stimulation of Na+, K+-ATPase and 5′-nucleotidase5 relate to the cell membrane. We report here that PMA alters the cell surface protein composition of chick embryo fibroblasts, causing a decrease in the major surface protein LETS (molecular weight 250,000). Previous work by several laboratories has indicated that LETS, which is present on the surface of fibroblasts from a variety of species, either decreases or disappears upon transformation6–11. Although LETS is highly sensitive to cleavage by proteases such as plasmin12, its mechanism of loss following transformation remains to be clarified. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print issues and online access $199.00 per year only $3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CORNIFICATION OF KERATINOCYTES IS ASSOCIATED WITH DIFFERENTIAL CHANGES IN THE CATALYTIC ACTIVITY AND THE IMMUNOREACTIVITY OF TRANSGLUTAMINASE-1 Article Open access 06 December 2023 ALOE POLYSACCHARIDE PROMOTES KERATINOCYTE PROLIFERATION, MIGRATION, AND DIFFERENTIATION BY UPREGULATING THE EGFR/PKC-DEPENDENT SIGNALING PATHWAYS Article Open access 10 March 2025 PLASMA MEMBRANE EFFECTS OF SPHINGOLIPID-SYNTHESIS INHIBITION BY MYRIOCIN IN CHO CELLS: A BIOPHYSICAL AND LIPIDOMIC STUDY Article Open access 19 January 2022 REFERENCES * Berenblum, I., in _Cancer_, 1 (edit. by Becker, F. F.), 323–344 (Plenum, New York, 1975). Google Scholar  * Hecker, E., _Meth. Cancer Res._, 6, 439–484 (1971). CAS  Google Scholar  * Van Duuren, B. L., _Prog. exp. Tumor Res._, 11, 31–68 (1969). Article  CAS  PubMed  Google Scholar  * Rohrschneider, L. R., and Boutwell, R. K., _Cancer Res._, 33, 1945–1952 (1973). CAS  PubMed  Google Scholar  * Sivak, A., Mossman, B. T., and Van Duuren, B. L., _Biochem. biophys. Res. Commun._, 46, 605–609 (1972). Article  CAS  PubMed  Google Scholar  * Robbins, P. W. _et al._ _Cold Spring Harb. Symp.quant. Biol._, 39, 1173–1180 (1974). Article  Google Scholar  * Hynes, R. O., _Proc. natn. Acad. Sci. U.S.A._, 70, 3170–3174 (1973). Article  CAS  ADS  Google Scholar  * Hynes, R. O., and Wyke, J. A., _Virology_, 64, 492–504 (1975). Article  CAS  PubMed  Google Scholar  * Vaheri, A., and Ruoslahti, E., _Int. J. Cancer_, 13, 579–586 (1974). Article  CAS  PubMed  Google Scholar  * Gahmberg, C. G., Kiehn, D., and Hakomori, S. I., _Nature_, 248, 413–415 (1974). Article  CAS  ADS  PubMed  Google Scholar  * Yamada, K. M., and Weston, J. A., _Proc. natn. Acad. Sci. U.S.A._, 71, 3492–3496 (1974). Article  CAS  ADS  Google Scholar  * Blumberg, P. M., and Robbins, P. W., _Cell_, 6, 137–147 (1975). Article  CAS  PubMed  Google Scholar  * Estensen, R. D., Hadden, J. W., Hadden, E. M., Touraine, F., Touraine, J. L., Haddox, M. K., and Goldberg, N. D., in _Control of Proliferation in Animal Cells_ (edit. by Clarkson, B., and Baserga, R.), 627–634 (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1974). Google Scholar  * Jacobson, K., Wenner, C. E., Kemp, G., and Papahadjopoulos, D., _Cancer Res._, 35, 2991–2995 (1975). CAS  PubMed  Google Scholar  * Wigler, M., and Weinstein, I. B., _Nature_, 259, 232–233 (1976). Article  CAS  ADS  PubMed  Google Scholar  * Sivak, A., _J. cell. Physiol_, 80, 167–174 (1972). Article  CAS  PubMed  Google Scholar  * Belman, S., and Troll, W., _Cancer Res._, 34, 3446–3455 (1974). CAS  PubMed  Google Scholar  * Diamond, L., O'Brien, S., Donaldson, C., and Shimizu, Y., _Int. J. Cancer_, 13, 721–730 (1974). Article  CAS  PubMed  Google Scholar  * Mondal, S., Brankow, D. W., and Heidelberger, C., _Cancer Res._, 36, 2254–2260 (1976). CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115 PETER M. BLUMBERG, PAUL E. DRIEDGER & PETER W. ROSSOW Authors * PETER M. BLUMBERG View author publications You can also search for this author inPubMed Google Scholar * PAUL E. DRIEDGER View author publications You can also search for this author inPubMed Google Scholar * PETER W. ROSSOW View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE BLUMBERG, P., DRIEDGER, P. & ROSSOW, P. Effect of a phorbol ester on a transformation-sensitive surface protein of chick fibroblasts. _Nature_ 264, 446–447 (1976). https://doi.org/10.1038/264446a0 Download citation * Received: 12 July 1976 * Accepted: 12 October 1976 * Issue Date: 02 December 1976 * DOI: https://doi.org/10.1038/264446a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT PMA (phorbol myristate acetate) is the most active of a class of compounds present in croton oil which act as tumour promoters1–3. While PMA possesses little car-cinogenicity in its


own night, its repeated application to mouse skin causes tumour induction in animals treated up to several months previously with a single subthreshold dose of a carcinogen. If the order of


treatments is reversed, that is, if PMA treatment precedes that with the carcinogen, then no tumours are induced. Studies both with mouse skin and with cells in tissue culture indicate


substantial effects of PMA on cell behaviour and biochemistry. Many of these effects such as alteration of phospholipid synthesis4 or stimulation of Na+, K+-ATPase and 5′-nucleotidase5


relate to the cell membrane. We report here that PMA alters the cell surface protein composition of chick embryo fibroblasts, causing a decrease in the major surface protein LETS (molecular


weight 250,000). Previous work by several laboratories has indicated that LETS, which is present on the surface of fibroblasts from a variety of species, either decreases or disappears upon


transformation6–11. Although LETS is highly sensitive to cleavage by proteases such as plasmin12, its mechanism of loss following transformation remains to be clarified. Access through your


institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 51 print


issues and online access $199.00 per year only $3.90 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to


local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT


BEING VIEWED BY OTHERS CORNIFICATION OF KERATINOCYTES IS ASSOCIATED WITH DIFFERENTIAL CHANGES IN THE CATALYTIC ACTIVITY AND THE IMMUNOREACTIVITY OF TRANSGLUTAMINASE-1 Article Open access 06


December 2023 ALOE POLYSACCHARIDE PROMOTES KERATINOCYTE PROLIFERATION, MIGRATION, AND DIFFERENTIATION BY UPREGULATING THE EGFR/PKC-DEPENDENT SIGNALING PATHWAYS Article Open access 10 March


2025 PLASMA MEMBRANE EFFECTS OF SPHINGOLIPID-SYNTHESIS INHIBITION BY MYRIOCIN IN CHO CELLS: A BIOPHYSICAL AND LIPIDOMIC STUDY Article Open access 19 January 2022 REFERENCES * Berenblum, I.,


in _Cancer_, 1 (edit. by Becker, F. F.), 323–344 (Plenum, New York, 1975). Google Scholar  * Hecker, E., _Meth. Cancer Res._, 6, 439–484 (1971). CAS  Google Scholar  * Van Duuren, B. L.,


_Prog. exp. Tumor Res._, 11, 31–68 (1969). Article  CAS  PubMed  Google Scholar  * Rohrschneider, L. R., and Boutwell, R. K., _Cancer Res._, 33, 1945–1952 (1973). CAS  PubMed  Google Scholar


  * Sivak, A., Mossman, B. T., and Van Duuren, B. L., _Biochem. biophys. Res. Commun._, 46, 605–609 (1972). Article  CAS  PubMed  Google Scholar  * Robbins, P. W. _et al._ _Cold Spring Harb.


Symp.quant. Biol._, 39, 1173–1180 (1974). Article  Google Scholar  * Hynes, R. O., _Proc. natn. Acad. Sci. U.S.A._, 70, 3170–3174 (1973). Article  CAS  ADS  Google Scholar  * Hynes, R. O.,


and Wyke, J. A., _Virology_, 64, 492–504 (1975). Article  CAS  PubMed  Google Scholar  * Vaheri, A., and Ruoslahti, E., _Int. J. Cancer_, 13, 579–586 (1974). Article  CAS  PubMed  Google


Scholar  * Gahmberg, C. G., Kiehn, D., and Hakomori, S. I., _Nature_, 248, 413–415 (1974). Article  CAS  ADS  PubMed  Google Scholar  * Yamada, K. M., and Weston, J. A., _Proc. natn. Acad.


Sci. U.S.A._, 71, 3492–3496 (1974). Article  CAS  ADS  Google Scholar  * Blumberg, P. M., and Robbins, P. W., _Cell_, 6, 137–147 (1975). Article  CAS  PubMed  Google Scholar  * Estensen, R.


D., Hadden, J. W., Hadden, E. M., Touraine, F., Touraine, J. L., Haddox, M. K., and Goldberg, N. D., in _Control of Proliferation in Animal Cells_ (edit. by Clarkson, B., and Baserga, R.),


627–634 (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1974). Google Scholar  * Jacobson, K., Wenner, C. E., Kemp, G., and Papahadjopoulos, D., _Cancer Res._, 35, 2991–2995


(1975). CAS  PubMed  Google Scholar  * Wigler, M., and Weinstein, I. B., _Nature_, 259, 232–233 (1976). Article  CAS  ADS  PubMed  Google Scholar  * Sivak, A., _J. cell. Physiol_, 80,


167–174 (1972). Article  CAS  PubMed  Google Scholar  * Belman, S., and Troll, W., _Cancer Res._, 34, 3446–3455 (1974). CAS  PubMed  Google Scholar  * Diamond, L., O'Brien, S.,


Donaldson, C., and Shimizu, Y., _Int. J. Cancer_, 13, 721–730 (1974). Article  CAS  PubMed  Google Scholar  * Mondal, S., Brankow, D. W., and Heidelberger, C., _Cancer Res._, 36, 2254–2260


(1976). CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pharmacology, Harvard Medical School, Boston, Massachusetts, 02115 PETER


M. BLUMBERG, PAUL E. DRIEDGER & PETER W. ROSSOW Authors * PETER M. BLUMBERG View author publications You can also search for this author inPubMed Google Scholar * PAUL E. DRIEDGER View


author publications You can also search for this author inPubMed Google Scholar * PETER W. ROSSOW View author publications You can also search for this author inPubMed Google Scholar RIGHTS


AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE BLUMBERG, P., DRIEDGER, P. & ROSSOW, P. Effect of a phorbol ester on a transformation-sensitive surface


protein of chick fibroblasts. _Nature_ 264, 446–447 (1976). https://doi.org/10.1038/264446a0 Download citation * Received: 12 July 1976 * Accepted: 12 October 1976 * Issue Date: 02 December


1976 * DOI: https://doi.org/10.1038/264446a0 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not


currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative