Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 Mar;65(3):586–591. doi: 10.1172/JCI109703

Binding of Retinoids to Human Breast Cancer Cell Lines and their Effects on Cell Growth

Andre Lacroix 1, Marc E Lippman 1
PMCID: PMC371399  PMID: 7188772

Abstract

Vitamin A and its analogues (retinoids) regulate the differentiation of epithelial tissues. Retinoids inhibit the induction of rat mammary cancers by carcinogens in vivo, and cellular binding proteins for retinoids have been demonstrated in some human breast cancer samples. In this study, we examined the model system of human breast cancer cell lines in long-term tissue culture for effects of retinoids on growth and for the presence of cellular retinoid binding proteins. Retinoic acid and retinol inhibit the growth of of MCF-7, Hs578T, and ZR-75-B cell lines. Retinoic acid is more potent than retinol in this regard: 50% growth inhibition is achieved by 6 nM retinoic acid in ZR-75-B and by 700 nM in MCF-7 and Hs578T, whereas 5-8 μM retinol is required in all three cell lines. The time to onset of growth inhibition varies markedly between cell lines and is not related to cell density or doubling time. Retinoic acid increases the doubling time of MCF-7 and ZR-75-B by two- to threefold, but causes cell death in Hs578T. The growth inhibition is reversible in every cell line by removal of retinoic acid. Specific and distinct binding of [3H]retinoic acid and [3H]retinol is present in cytosols of MCF-7 and Hs578T cells as assessed by sucrose density gradient centrifugation. In ZR-75-B, [3H]retinoic acid binding was present, but no binding of [3H]retinol was detectable. This study reveals that retinoids may play an important role in the regulation and treatment of human breast cancer and that human breast cancer cell lines represent a useful model to study this role.

Full text

PDF
586

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chytil F., Ong D. E. Mediation of retinoic acid-induced growth and anti-tumour activity. Nature. 1976 Mar 4;260(5546):49–51. doi: 10.1038/260049a0. [DOI] [PubMed] [Google Scholar]
  2. Dion L. D., Blalock J. E., Gifford G. E. Vitamin A-induced density-dependent inhibition of L-cell proliferation. J Natl Cancer Inst. 1977 Mar;58(3):795–801. doi: 10.1093/jnci/58.3.795. [DOI] [PubMed] [Google Scholar]
  3. Engel L. W., Young N. A., Tralka T. S., Lippman M. E., O'Brien S. J., Joyce M. J. Establishment and characterization of three new continuous cell lines derived from human breast carcinomas. Cancer Res. 1978 Oct;38(10):3352–3364. [PubMed] [Google Scholar]
  4. Grubbs C. J., Moon R. C., Sporn M. B., Newton D. L. Inhibition of mammary cancer by retinyl methyl ether. Cancer Res. 1977 Feb;37(2):599–602. [PubMed] [Google Scholar]
  5. Hackett A. J., Smith H. S., Springer E. L., Owens R. B., Nelson-Rees W. A., Riggs J. L., Gardner M. B. Two syngeneic cell lines from human breast tissue: the aneuploid mammary epithelial (Hs578T) and the diploid myoepithelial (Hs578Bst) cell lines. J Natl Cancer Inst. 1977 Jun;58(6):1795–1806. doi: 10.1093/jnci/58.6.1795. [DOI] [PubMed] [Google Scholar]
  6. Huber P. R., Geyer E., Küng W., Matter A., Torhorst J., Eppenberger U. Retinoic acid-binding protein in human breast cancer and dysplasia. J Natl Cancer Inst. 1978 Dec;61(6):1375–1378. [PubMed] [Google Scholar]
  7. Jetten A. M., Jetten M. E. Possible role of retinoic acid binding protein in retinoid stimulation of embryonal carcinoma cell differentiation. Nature. 1979 Mar 8;278(5700):180–182. doi: 10.1038/278180a0. [DOI] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Lotan R. Different susceptibilities of human melanoma and breast carcinoma cell lines to retinoic acid-induced growth inhibition. Cancer Res. 1979 Mar;39(3):1014–1019. [PubMed] [Google Scholar]
  10. Lotan R., Nicolson G. L. Inhibitory effects of retinoic acid or retinyl acetate on the growth of untransformed, transformed, and tumor cells in vitro. J Natl Cancer Inst. 1977 Dec;59(6):1717–1722. doi: 10.1093/jnci/59.6.1717. [DOI] [PubMed] [Google Scholar]
  11. Moon R. C., Grubbs C. J., Sporn M. B. Inhibition of 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis by retinyl acetate. Cancer Res. 1976 Jul;36(7 Pt 2):2626–2630. [PubMed] [Google Scholar]
  12. Moon R. C., Thompson H. J., Becci P. J., Grubbs C. J., Gander R. J., Newton D. L., Smith J. M., Phillips S. L., Henderson W. R., Mullen L. T. N-(4-Hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat. Cancer Res. 1979 Apr;39(4):1339–1346. [PubMed] [Google Scholar]
  13. Ong D. E., Chytil F. Presence of cellular rentinol and retinoic acid binding proteins in experimental rumors. Cancer Lett. 1976 Sep;2(1):25–30. doi: 10.1016/s0304-3835(76)80006-7. [DOI] [PubMed] [Google Scholar]
  14. Ong D. E., Page D. L., Chytil F. Retinoic acid binding protein: occurrence in human tumors. Science. 1975 Oct 3;190(4209):60–61. doi: 10.1126/science.1166300. [DOI] [PubMed] [Google Scholar]
  15. Rettura G., Schittek A., Hardy M., Levenson S. M., Demetriou A., Seifter E. Antitumor action of vitamin A in mice inoculated with adenocarcinoma cells. J Natl Cancer Inst. 1975 Jun;54(6):1489–1491. doi: 10.1093/jnci/54.6.1489. [DOI] [PubMed] [Google Scholar]
  16. Roels O. A. Vitamin A physiology. JAMA. 1970 Nov 9;214(6):1097–1102. [PubMed] [Google Scholar]
  17. Saari J. C., Futterman S., Stubbs G. W., Heffernan J. T., Bredberg L., Chan D. Y., Albert D. M. Cellular retinol- and retinoic acid-binding proteins in transformed mammalian cells. Invest Ophthalmol Vis Sci. 1978 Oct;17(10):988–992. [PubMed] [Google Scholar]
  18. Sani B. P., Donovan M. K. Localization of retinoic acid-binding protein in nuclei and the nuclear uptake of retinoic acid. Cancer Res. 1979 Jul;39(7 Pt 1):2492–2496. [PubMed] [Google Scholar]
  19. Sanl B. P., Corbett T. H. Retinoic acid-binding protein in normal tissues and experimental tumors. Cancer Res. 1977 Jan;37(1):209–213. [PubMed] [Google Scholar]
  20. Smith J. E., Milch P. O., Muto Y., Goodman D. S. The plasma transport and metabolism of retinoic acid in the rat. Biochem J. 1973 Apr;132(4):821–827. doi: 10.1042/bj1320821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Soule H. D., Vazguez J., Long A., Albert S., Brennan M. A human cell line from a pleural effusion derived from a breast carcinoma. J Natl Cancer Inst. 1973 Nov;51(5):1409–1416. doi: 10.1093/jnci/51.5.1409. [DOI] [PubMed] [Google Scholar]
  22. Sporn M. B., Dunlop N. M., Newton D. L., Henderson W. R. Relationships between structure and activity of retinoids. Nature. 1976 Sep 9;263(5573):110–113. doi: 10.1038/263110a0. [DOI] [PubMed] [Google Scholar]
  23. Sporn M. B., Dunlop N. M., Newton D. L., Smith J. M. Prevention of chemical carcinogenesis by vitamin A and its synthetic analogs (retinoids). Fed Proc. 1976 May 1;35(6):1332–1338. [PubMed] [Google Scholar]
  24. Sporn M. B., Newton D. L. Chemoprevention of cancer with retinoids. Fed Proc. 1979 Oct;38(11):2528–2534. [PubMed] [Google Scholar]
  25. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
  26. Takase S., Ong D. E., Chytil F. Cellular retinol-binding protein allows specific interaction of retinol with the nucleus in vitro. Proc Natl Acad Sci U S A. 1979 May;76(5):2204–2208. doi: 10.1073/pnas.76.5.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wiggert B., Russell P., Lewis M., Chader G. Differential binding to soluble nuclear receptors and effects on cell viability of retinol and retinoic acid in cultured retinoblastoma cells. Biochem Biophys Res Commun. 1977 Nov 7;79(1):218–225. doi: 10.1016/0006-291x(77)90083-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES