Cancer Cell Biology
EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2
Article first published online: 28 SEP 2004
Copyright © 2004 Wiley-Liss, Inc.
International Journal of Cancer
Volume 113, Issue 4, pages 561–567, 10 February 2005
How to Cite
Oosterhoff, J. K., Kühne, L. C., Grootegoed, J. A. and Blok, L. J. (2005), EGF signalling in prostate cancer cell lines is inhibited by a high expression level of the endocytosis protein REPS2. Int. J. Cancer, 113: 561–567. doi: 10.1002/ijc.20612
- Issue published online: 30 NOV 2004
- Article first published online: 28 SEP 2004
- Manuscript Accepted: 22 JUL 2004
- Manuscript Received: 19 FEB 2004
- The Netherlands Organisation for Health Research and Development. Grant Number: 903-46-179
- prostate cancer;
- EGF signalling
In advanced prostate cancer, cellular changes occur leading to a transition from androgen-dependent to androgen-independent growth. During this transition, proliferation of androgen-dependent prostate cancer cells becomes more and more dependent on growth factors, like the epidermal growth factor (EGF). Endocytosis of growth factor receptors, one of the mechanisms that controls growth factor signalling, was observed to be markedly changed in advanced metastatic prostate cancer. Internalisation and signalling of EGF receptors was examined in different prostate cancer cell lines, in relation to the expression level of the endocytosis-related REPS2 gene. It was observed that a high level of REPS2 correlates with reduced EGF-internalisation. To investigate this more thoroughly, prostate cancer cells with inducible REPS2 expression were generated. Using these cells, it was found that REPS2-induction indeed results in reduction of EGF-internalisation. Furthermore, when EGF receptor signalling was evaluated, by examination of mRNA expression for several EGF-responsive genes (EGF receptor, EGR-1, Fos and Jun), it was observed that induced expression of REPS2 exerts an inhibiting effect on this signalling. From these experiments, it is concluded that increased REPS2 expression negatively affects EGF receptor internalisation and subsequent signalling. Therefore, decreased REPS2 expression during prostate cancer progression, observed in earlier work, may result in enhanced EGF receptor expression and signalling, which could add to the androgen-independent state of advanced prostate cancer.