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The role of protein kinase PAK1 in the regulation of estrogen-independent growth of breast cancer

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Abstract

The major goal of this work was to study the intracellular signaling pathways responsible for the development of hormone resistance and maintenance of the autonomous growth of breast cancer cells. Particularly, the role of PAK1 (p21-activated kinase 1), the key mitogenic signaling protein has been analyzed in the context of the development of cell resistance to estrogens. In vitro studies were performed on cultured breast cancer cell lines: estrogen-dependent estrogen receptor (ER)-positive MCF-7 cells and estrogen-resistant ER-negative HBL-100 cells. We found that the resistant HBL-100 cells were characterized by a higher level of PAK1 and demonstrated PAK1 involvement in the maintenance of estrogen-independent cell growth. Studying downstream signaling pathways activated by PAK1, we have found Snail1, an epithelial-mesenchymal transition protein, as one of PAK1 effectors and obtained experimental evidence for importance of Snail1 in the regulation of cell proliferation. In general, the results obtained in this study demonstrate involvement of PAK1 and Snail1 in the formation of estrogen-independent phenotype of breast cancer cells thus showing the potential role of both proteins as markers of hormone resistance of breast tumors.

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References

  1. Krasil’nikov, M.A., Vopr. onkol., 2004, vol. 50, pp. 399–405.

    Google Scholar 

  2. Normanno, N., Di Maio, M., De Maio, E., De Luca, A., de Matteis, A., et al., Endocr. Relat. Cancer, 2005, vol. 12, pp. 721–747.

    Article  CAS  Google Scholar 

  3. Clarke, R., Liu, M.C., Bouker, K.B., Gu, Z., Lee, R.Y., et al., Oncogene, 2003, vol. 22, pp. 7316–7339.

    Article  CAS  Google Scholar 

  4. Jordan, V.C., Ann. Oncol., 2003, vol. 14, pp. 969–970.

    Article  CAS  Google Scholar 

  5. Jalava, P., Kuopio, T., Huovinen, R., Laine, J., and Collan, Y., Anticancer Res., 2005, vol. 25, pp. 2535–2542.

    CAS  Google Scholar 

  6. Henderson, B.E., Ponder, B.A.J., and Ross, R.K., Hormones, Genes and Cancer New York: Oxford University Press, p. 120–139.

  7. Kichina, J.V., Goc, A., Al-Husein, B., Somanath, P.R., and Kandel, E.S., Expert Opin. Ther. Targets, 2010, vol. 14, pp. 703–725.

    Article  CAS  Google Scholar 

  8. Molli, P.R., Li, D.Q., Murray B.W., Rayala, S.K., and Kumar, R., Oncogene, 2009, vol. 28, pp. 2545–2555.

    Article  CAS  Google Scholar 

  9. Ghosh, A., Awasthi, S., Peterson, J.R., and Hamburger, A.W., Br. J. Cancer, 2013, vol. 108, pp. 557–563.

    Article  CAS  Google Scholar 

  10. Kok, M., Zwart, W., Holm, C., Fles, R., Hauptmann, M., et al., Breast Cancer Research and Treatment, 2011, vol. 125, pp. 1–12.

    Article  CAS  Google Scholar 

  11. Bostner, J., Skoog, L., Fornander, T., Nordenskjold, B., and Stal, O., Clinical Cancer Research, 2010, vol. 16, pp. 1624–1633.

    Article  CAS  Google Scholar 

  12. Arias-Romero, L.E. and Chernoff, J., Small GTPases, 2010, vol. 1, pp. 124–128.

    Article  Google Scholar 

  13. Yang, Y., Du, J., Hu, Z., Liu, J., Tian, Y., et al., J. Biomed. Res., 2011, vol. 25, pp. 237–245.

    Article  CAS  Google Scholar 

  14. Krasil’nikov, M.A., Shatskaya, V.A., Stavrovskaya, A.A., Erohina, M., Gershtein, E.S., et al. Biochim. Biophys. Acta, 1999, vol. 1450, pp. 434–443.

    Article  Google Scholar 

  15. Reid, G., Hubner, M.R., Metivier, R., Brand, H., Denger, S., et al., Mol. Cell, 2003, vol. 11, pp. 695–707.

    Article  CAS  Google Scholar 

  16. Vincent, T., Neve, E.P., Johnson, J.R., Kukalev, A., Rojo, F., et al., Nat. Cell Biol., 2009, vol. 11, pp. 943–950.

    Article  CAS  Google Scholar 

  17. Lobanova, Y.S., Scherbakov, A.M., Shatskaya, V.A., Evteev, V.A., and Krasil’nikov, M.A., Mol. Cell Biochem., 2009, vol. 324, pp. 65–71.

    Article  CAS  Google Scholar 

  18. Scherbakov, A.M., Andreeva, O.E., Shatskaya, V.A., and Krasil’nikov, M.A., J. Cell. Biochem., 2012, vol. 113, pp. 2147–2155.

    Article  CAS  Google Scholar 

  19. Dhasarathy, A., Kajita, M., and Wade, P.A., Mol. Endocrinol., 2007, vol. 21, pp. 2907–2918.

    Article  CAS  Google Scholar 

  20. Fujita, N., Jaye, D.L., Kajita, M., Geigerman, C., Moreno, C.S., et al., Cell, 2003, vol. 113, pp. 207–219.

    Article  CAS  Google Scholar 

  21. Sells, M.A., Knaus, U.G., Bagrodia, S., Ambrose, D.M., Bokoch, G.M., and Chernoff, J., Curr. Biol., 1997, vol. 7, pp. 202–210.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Blokhin Russian Research Cancer Center, Kashirskoye sh. 24, Moscow, 115478, Russia

    E. A. Avilova, O. E. Andreeva, V. A. Shatskaya & M. A. Krasil’nikov

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  1. E. A. Avilova
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  2. O. E. Andreeva
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  3. V. A. Shatskaya
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  4. M. A. Krasil’nikov
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Correspondence to E. A. Avilova.

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Original Russian Text © E.A. Avilova, O.E. Andreeva, V.A. Shatskaya, M.A. Krasil’nikov, 2015, published in Biomeditsinskaya Khimiya.

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Avilova, E.A., Andreeva, O.E., Shatskaya, V.A. et al. The role of protein kinase PAK1 in the regulation of estrogen-independent growth of breast cancer. Biochem. Moscow Suppl. Ser. B 9, 58–62 (2015). https://doi.org/10.1134/S1990750815010023

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  • DOI: https://doi.org/10.1134/S1990750815010023

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