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Article

The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms

  • Authors:
    • Marianna Lauricella
    • Daniela Carlisi
    • Michela Giuliano
    • Giuseppe Calvaruso
    • Cesare Cernigliaro
    • Renza Vento
    • Antonella D'Anneo
  • View Affiliations / Copyright

    Affiliations: Department of Experimental Biomedicine and Clinical Neurosciences, Laboratory of Biochemistry, University of Palermo, Palermo, Italy, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, Laboratory of Biochemistry, University of Palermo, Palermo, Italy
  • Pages: 352-360
    |
    Published online on: April 21, 2016
       https://doi.org/10.3892/ijo.2016.3495
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Abstract

Breast cancer stem cells seem to play important roles in breast tumor recurrence and endocrine therapy resistance, although the underlying mechanisms have not been well established. Moreover, in some tumor systems the immunosurveillance failure against cancer cells has been related to the presence of the granzyme B inhibitor PI-9. This study explored the status of PI-9 in tumorspheres isolated from estrogen receptor-α positive (ERα+) breast cancer MCF7 cells. Studies were performed in tertiary tumorspheres which possess high levels of stemness markers (Nanog, Oct3/4 and Sox2) and self-renewal ability. The exposure to estrogens (17-β estradiol and genistein) increased the number and sizes of tumorspheres, promoting cell proliferation as demonstrated by the increase in the proliferating cell nuclear antigen (PCNA). The study of the three isoforms (66, 46 and 36 kDa) of ERα disclosed that tertiary tumorspheres exhibit a marked increase in ERα36, while the level of ERα66, which is highly expressed in MCF7 cells, declines. Although it is known that PI-9 is a transcriptional target of ERα66, surprisingly in tertiary tumorspheres, despite the reduced level of ERα66, the protein and mRNA content of PI-9 is higher than in MCF7 cells. Treatment with estrogens further increased PI-9 level while decreased that of ERα66 isoform thus excluding the involvement of this receptor isoform in the event. Moreover, our studies also provided evidence that tertiary tumorspheres express elevated levels of CXCR4 and phospho-p38, suggesting that the high PI-9 content might be ascribed to the activation of the proliferative CXCR4/phospho-p38 axis. Taken together, these events could supply a selective advantage to breast cancer stem cells by interfering with immunosurveillance systems and open up the avenue to new possible targets for breast cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Lauricella M, Carlisi D, Giuliano M, Calvaruso G, Cernigliaro C, Vento R and D'Anneo A: The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. Int J Oncol 49: 352-360, 2016.
APA
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., & D'Anneo, A. (2016). The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. International Journal of Oncology, 49, 352-360. https://doi.org/10.3892/ijo.2016.3495
MLA
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., D'Anneo, A."The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms". International Journal of Oncology 49.1 (2016): 352-360.
Chicago
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., D'Anneo, A."The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms". International Journal of Oncology 49, no. 1 (2016): 352-360. https://doi.org/10.3892/ijo.2016.3495
Copy and paste a formatted citation
x
Spandidos Publications style
Lauricella M, Carlisi D, Giuliano M, Calvaruso G, Cernigliaro C, Vento R and D'Anneo A: The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. Int J Oncol 49: 352-360, 2016.
APA
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., & D'Anneo, A. (2016). The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms. International Journal of Oncology, 49, 352-360. https://doi.org/10.3892/ijo.2016.3495
MLA
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., D'Anneo, A."The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms". International Journal of Oncology 49.1 (2016): 352-360.
Chicago
Lauricella, M., Carlisi, D., Giuliano, M., Calvaruso, G., Cernigliaro, C., Vento, R., D'Anneo, A."The analysis of estrogen receptor-α positive breast cancer stem-like cells unveils a high expression of the serpin proteinase inhibitor PI-9: Possible regulatory mechanisms". International Journal of Oncology 49, no. 1 (2016): 352-360. https://doi.org/10.3892/ijo.2016.3495
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