Mechanisms of androgen-independent Prostate Cancer Progression : Which Way to Go?
(Mechanismen van progressie van androgeen-onafhankelijke prostaatkanker : Langs Welke Weg?)
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Prostate cancer has a high incidence in the western world. Early detection of the disease is crucial for successful management, since late stages of the disease cannot be cured. Unfortunately, however, conventional detection through rising PSA levels is already too late in one-third of the cases. These patients have metastatic disease, which can only be treated temporarily by androgen ablation therapy. The main problem of metastatic prostate cancer is a transition from initially androgen-dependent growth to androgen-independent growth. Androgen-independence of prostate cancer cells implies resistance to androgen ablation therapy, eventually leading to death of the patient. Next to androgens, many other growth and differentiation inducing factors play a role during development and homeostasis of the prostate and during progression of prostate cancer. Peptide growth factors like EGF, TGF-a, FGF, IGF, NGF, PDGF, VEGF, and TGF-ß have all been hypothesized to be involved in prostate cancer growth. The proposed mechanism of androgen-independent prostate cancer progression is through stimulation of proliferation via these factors as compensation for lack of proliferation stimulation through androgens. Furthermore, crosstalk between androgen signalling and growth factor signalling seems to play a role in prostate cancer growth. Growth factors are reported to activate androgen receptors and androgens to induce growth factor and growth factor receptor expression. In this thesis we focussed mainly on EGF signalling. First, because REPS2, a protein potentially involved in androgen-independent prostate cancer, acts through affecting EGF signalling, and second, because gene profiling indicated that EGF and androgen signalling seem to intertwine in androgen-independent prostate cancer.
Netherlands Organization for Health Research and Development
J.E. Jurriaanse Stichting
Dr. Ir.van de Laar Strichting
Grotegoed, Prof. Dr. J.A. (promotor)
- prostate cancer
- prostate cancer cells
- reps 2
- lncap cells
- prostate cancer progression
- egf receptor