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Endocrine

, Volume 16, Issue 1, pp 7–14 | Cite as

The endogenous progesterone metabolite, 5α-pregnane-3,20-dione, decreases cell-substrate attachment, adhesion plaques, vinculin expression, and polymerized F-actin in MCF-7 breast cancer cells

  • John P. WiebeEmail author
  • David Muzia
Article

Abstract

Tumorous human breast tissue readily converts progesterone to 5α-pregnane-3,20-dione (5αP), and this metabolite has been shown to stimulate proliferation and to decrease adhesion of MCF-7 breast cancer cells. To determine the mechanisms of action of 5αP on cell adhesion, MCF-7 cells were grown without or with 5αP (10−9–10−5 M), and the effects on cell and nuclear morphology, adhesion plaques, vinculin and actin expression, actin polymerization, and microfilament distribution were examined by immunohistochemistry, morphometry (using confocal microscopy and digital computer imaging analysis), and Western blotting. Treatment of cells with 10−9–10−6 M 5αP resulted in dose-dependent decreases in cell area, cell-to-cell contacts, and attachment to the substratum, and increases in variation in nuclear area. These changes in the 5αP-treated cells were accompanied by decreases in vinculin-containing adhesion plaques, vinculin expression, polymerized actin stress fibers, and decreases in insoluble and increases in soluble actin fractions. The results suggest that the observed decreases in adhesion and increases in cell proliferation following 5αP treatment may be owing to depolymerization of actin and decreased expression of actin and vinculin. We conclude that the endogenous progesterone metabolite, 5αP, may be involved in promoting breast neoplasia and metastasis by affecting adhesion and cytoskeletal molecules.

Key Words

Progesterone metabolite 5α-pregnane-3,20-dione breast cancer adhesion plaques vinculin actin 

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References

  1. 1.
    Going, J. J., Anderson, T.J., Battersby, S., and MacIntyre, C. C. A. (1988). Am. J. Pathol. 130, 193–204.PubMedGoogle Scholar
  2. 2.
    Potten, C. S., Watson, R. J., Williams, G. T., Tickle, S., Roberts, S. A., Harris, M., and Howel, A. (1988). Br. J. Cancer 58, 163–170.PubMedGoogle Scholar
  3. 3.
    Pike, M. C., Spicer, D. V., Dahmoush, L., and Press, M. F. (1993). Epidemiol. Rev. 15, 17–35.PubMedGoogle Scholar
  4. 4.
    King, R. J. B. (1991). J. Steroid Biochem. Mol. Biol. 39, 811–818.PubMedCrossRefGoogle Scholar
  5. 5.
    Santen, R. J., Manni, A., Harvey, H., and Redmond, C. (1990). Endocr. Rev. 11, 221–265.PubMedCrossRefGoogle Scholar
  6. 6.
    Anderson, T. J., Battersby, S., King, R. J. B., McPherson, K., and Going, J. J. (1989). Hum. Pathol. 20, 1139–1144.PubMedCrossRefGoogle Scholar
  7. 7.
    Groshong, S. D., Owen, G. I., Grimison, B., Schauer, I. E., Todd, M. C., Langan, T. A., Sclafani, R. A., Lange, C. A., and Horwitz, K. B. (1997). Mol. Endocrinol. 11, 1593–1607.PubMedCrossRefGoogle Scholar
  8. 8.
    Braunsberg, H., Coldham, N. G., Leake, R. E., Cowan, S. K., and Wong, W. R. (1987). Eur. J. Cancer Clin. Oncol. 23, 563–572.PubMedCrossRefGoogle Scholar
  9. 9.
    Clark, C. L. and Sutherland, R. L. (1990). Endocr. Rev. 11, 266–302.Google Scholar
  10. 10.
    Cappelletti, V., Miodini, P., Fioravanti, L., and Di Fronzo, G. (1995). Anticancer Res. 15, 2551–2556.PubMedGoogle Scholar
  11. 11.
    Musgrove, E. A. and Sutherland, R. L. (1994). Semin. Cancer Biol. 5, 381–389.PubMedGoogle Scholar
  12. 12.
    Wiebe, J. P., Muzia, D., Hu, J., Szwajcer, D., Hill, S. A., and Seachrist, J. L. (2000). Cancer Res. 60, 936–943.PubMedGoogle Scholar
  13. 13.
    Weiler, P. J. and Wiebe, J. P. (2000). Biochem. Biophys. Res. Commun. 272, 731–737.PubMedCrossRefGoogle Scholar
  14. 14.
    Fox, C. H., Caspersson, T., Kudynowski, J., Sanford, K. K., and Tarone, R. E. (1977). Cancer Res. 37, 892–897.PubMedGoogle Scholar
  15. 15.
    Folkman, J. and Moscona, A. (1978). Nature 273, 345–349.PubMedCrossRefGoogle Scholar
  16. 16.
    Baak, J. P., Van Dop, H., and Kurver, P. H. (1985). Cancer 56, 374–382.PubMedCrossRefGoogle Scholar
  17. 17.
    Iwig, M., Czeslick, E., Muller, A., Gruner, M., Spindler, M., and Glaesser, D. (1995). Eur. J. Cell Biol. 67, 145–157.PubMedGoogle Scholar
  18. 18.
    Dewhurst, L. O., Rennie, I. G., and MacNeil, S. (1998). Melanoma Res. 8, 303–311.PubMedCrossRefGoogle Scholar
  19. 19.
    Ben-Ze’ev, A. (1985). Biochim. Biophys. Acta 780, 197–212.PubMedGoogle Scholar
  20. 20.
    Holme, T. C. (1990). Eur. J. Surg. Oncol. 16, 161–169.PubMedGoogle Scholar
  21. 21.
    Lin, Z. X. (1993). Chin. J. Oncol. 15, 8–11.Google Scholar
  22. 22.
    Holth, L. T., Chadee, D. N., Spencer, V. A., Samuel, S. K., Safneck, J. R., and Davie, J. R. (1998). Int. J. Oncol. 13, 827–837.PubMedGoogle Scholar
  23. 23.
    Burridge, K. (1986). Cancer Rev. 4, 18–78.Google Scholar
  24. 24.
    Ráz, A. (1988). Ciba Found. Symp. 141, 109–122.PubMedGoogle Scholar
  25. 25.
    Suzuki, H., Nagata, H., Shimada, Y., and Konno, A. (1998). Int. J. Oncol. 12, 1079–1084.PubMedGoogle Scholar
  26. 26.
    Wilkins, J. A. and Lin, S. (1982). Cell 28, 83–90.PubMedCrossRefGoogle Scholar
  27. 27.
    Luna, E. J. and Hitt, A. L. (1992). Science 258, 955–964.PubMedCrossRefGoogle Scholar
  28. 28.
    Humphries, M. J. and Newham, P. (1998). Trends Cell Biol. 8, 78–83.PubMedCrossRefGoogle Scholar
  29. 29.
    Schliwa, M., Nakamura, T., Porter, K. R., and Euteneuer, V. (1984). J. Cell Biol. 99, 1045–1059.PubMedCrossRefGoogle Scholar
  30. 30.
    Sadano, H., Inoue, M., and Taniguchi, S. (1992). Jap. J. Cancer Res. 83, 625–630.Google Scholar
  31. 31.
    Sapino, A., Pietribiasi, F., Bussolati, G., and Marchisio, P. C. (1986). Cancer Res. 46, 2526–2531.PubMedGoogle Scholar
  32. 32.
    Koukouritaki, S. B., Margoris, A. N., Gravanis, A., Hartig, R., and Stournaras, C. (1997). J. Cell. Biochem. 65, 492–500.PubMedCrossRefGoogle Scholar
  33. 33.
    McCrohon, J. A., Jessup, W., Handelsman, D. J., and Celermajer, D. S. (1999). Circulation 99, 2317–2322.PubMedGoogle Scholar
  34. 34.
    DePasquale, J. A., Samsonoff, W. A., and Gierthy, J. F. (1994). J. Cell Sci. 107, 1241–1254.PubMedGoogle Scholar
  35. 35.
    Gronowicz, G. A. and McCarthy, M. B. (1995). Endocrinology 136, 598–608.PubMedCrossRefGoogle Scholar
  36. 36.
    Pearson, D. and Sheldon, P. (1995). Adv. Exp. Med. Biol. 371, 167–170.Google Scholar
  37. 37.
    Lin, V. C., Ng, E. H., Aw, S. E., Tan, M. G., Ng, E. H., and Bay, B. H. (2000). Mol. Endocrinol. 14, 348–358.PubMedCrossRefGoogle Scholar
  38. 38.
    Baak, J. P., Kurver, P. H., De Snoo-Niewlaat, A. J., De Graef, S., Makkink, B., and Boon, M. E. (1982). Histopathology 6, 327–339.PubMedCrossRefGoogle Scholar
  39. 39.
    Wittekind, C. and Schulte, E. (1987). Ann. Quant. Cytol. Histol. 9, 480–484.Google Scholar
  40. 40.
    Wolberg, W. H., Street, W. N., and Magasarian, O. L. (1997). Cancer 81, 172–179.PubMedCrossRefGoogle Scholar
  41. 41.
    Pokorna, E., Jordan, P. W., O’Neill, C. H., Zicha, D., Gilbert, C. S., and Vesely, P. (1994). Cell Motil. Cytoskel. 28, 25–33.CrossRefGoogle Scholar
  42. 42.
    Helige, C., Zellnig, G., Hoffman-Wellenhof, R., Fink-Puches, R., Smolle, J., and Tritthart, H. A. (1997). Invas. Metast. 17, 26–41.Google Scholar
  43. 43.
    Bershadsky, A. D., Gluck, U., Denisenko, O. N., Sklyarova, T. V., Spector, I., and Ben-Ze’ev, A. (1995). J. Cell Sci. 180, 1183–1193.Google Scholar
  44. 44.
    Hazan, R. B., Kang, L., Roe, S., Borgen, P. I., and Rimm, D. L. (1997). J. Biol. Chem. 272, 32,448–32,453.CrossRefGoogle Scholar
  45. 45.
    Berx, G., Nollet, F., and van Roy, F. (1998). Cell Adhes. Commun. 6, 171–184.PubMedCrossRefGoogle Scholar
  46. 46.
    Fujimoto, J., Ichigo, S., Hori, M., Morishita, S., and Tamaya, T. (1996). J. Steroid Biochem. Mol. Biol. 57, 275–282.PubMedCrossRefGoogle Scholar
  47. 47.
    Shi, Y. E., Liu, Y. E., Lippman, M. E., and Dickson, R. B. (1994). Hum. Reprod. 9(Suppl. 1), 162–173.PubMedGoogle Scholar
  48. 48.
    Wiebe, J. P., Deline, C., Buckingham, K. D., Dave, V., and Stothers, J. B. (1985). Steroids 45, 39–51.PubMedCrossRefGoogle Scholar
  49. 49.
    Marchevsky, A. M. and Erler, B. S. (1994). In: Image analysis: a primer for pathologists. Marchevsky. A. M. and Bartels, P. H. (eds.). Raven Press, New York, pp. 125–180.Google Scholar
  50. 50.
    Usson, Y., Guignandon, A., Laroche, N., Lafage-Proust, M. H., and Vico, L. (1997). Cytometry 28, 298–304.PubMedCrossRefGoogle Scholar
  51. 51.
    Bradford, M. M. (1976). Anal. Biochem. 72, 248–259.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc 2001

Authors and Affiliations

  1. 1.Hormonal Regulatory Mechanisms/Department of ZoologyUniversity of Western OntarioLondonCanada

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