In vitro modeling of HER2-targeting therapy in disseminated prostate cancer

  • Authors:
    • Jennie Andersson
    • Maria Rosestedt
    • Veronika Asplund
    • Nazila Yavari
    • Anna Orlova
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  • Published online on: August 29, 2014     https://doi.org/10.3892/ijo.2014.2628
  • Pages: 2153-2158
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Abstract

Prostate cancer (PCa) is the most common cancer type among men. Treatments against advanced PCa are limited and in many cases only palliative. In a later, androgent independent, stage of PCa androgen receptors can be activated without interaction with ligand, i.e., by receptors of tyrosine kinase (RTK) family in the outlaw pathway. Human epidermal growth factor receptors HER2 and EGFR belong to RTK-family. HER2 is one of the main actors in the outlaw pathway with EGFR as the preferable heterodimerizing partner. We hypothesized that information on HER2 expression in advanced PCa could be useful for selection of patients for anti-RTK therapy and monitoring of therapy response. A panel of PCa cell lines (LNCap, PC3, DU-145) was subjected to a 8-week treatment using drugs influencing the RTK: trastuzumab (anti‑HER2), 17-DMAG (Hsp90 inhibitor), alone or in combination, and their HER2 and EGFR expressions were compared with non-treated cells. Treatment with trastuzumab decreased proliferation of LNCap and DU-145 cell lines, while 17-DMAG and trastuzumab/17‑DMAG combination affected all three cell lines. HER2 expression was significantly increased in PC3 cells, the most resistant cell line. On the contrary, in responding cells (LNCap and DU-145) HER2 expression decreased, accompanied by increased EGFR expression. However, additional treatment of cells with cetuximab (anti‑EGFR) did not give any additive effect to trastuzumab. In this study the response to anti-RTK therapy proved to vary between different PCa cell lines. We have demonstrated that RTK targeting treatments may affect the phenotypic profile of PCa tumor cells that correlates with therapy outcome. Observation of such changes during treatment could be used for monitoring and an improved therapy outcome.
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November-2014
Volume 45 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Andersson J, Rosestedt M, Asplund V, Yavari N and Orlova A: In vitro modeling of HER2-targeting therapy in disseminated prostate cancer. Int J Oncol 45: 2153-2158, 2014
APA
Andersson, J., Rosestedt, M., Asplund, V., Yavari, N., & Orlova, A. (2014). In vitro modeling of HER2-targeting therapy in disseminated prostate cancer. International Journal of Oncology, 45, 2153-2158. https://doi.org/10.3892/ijo.2014.2628
MLA
Andersson, J., Rosestedt, M., Asplund, V., Yavari, N., Orlova, A."In vitro modeling of HER2-targeting therapy in disseminated prostate cancer". International Journal of Oncology 45.5 (2014): 2153-2158.
Chicago
Andersson, J., Rosestedt, M., Asplund, V., Yavari, N., Orlova, A."In vitro modeling of HER2-targeting therapy in disseminated prostate cancer". International Journal of Oncology 45, no. 5 (2014): 2153-2158. https://doi.org/10.3892/ijo.2014.2628