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REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells

Oncogene volume 22, pages 2920–2925 (2003)Cite this article

Abstract

During progression of prostate cancer, cellular changes occur, leading to a transition from androgen-dependent to androgen-independent growth. One aspect of this transition is a switch from androgens to growth factors, like epidermal growth factor (EGF), as primary regulators of proliferation. We examined the involvement of REPS2/POB1 in this process. REPS2/POB1 is an EH domain-containing protein, reported to be involved in signalling via RalBP1 and to play a role in endocytosis of EGF receptors. Furthermore, the protein is relatively highly expressed in androgen-dependent as compared to androgen-independent human prostate cancer cell lines and xenografts. Next to the known REPS2/POB1 protein, an open reading frame encoding REPS2/POB1, with 139 additional amino-acid residues at the NH2-terminus, was cloned and found to be expressed in prostate cancer cells. Overexpression, by transient transfection, of both forms of REPS2/POB1 in prostate cancer cell lines, induced apoptosis within 48 h. At shorter time intervals after transfection, signalling towards a TPA response element luciferase reporter was found to be inhibited. From these experiments, it is concluded that REPS2/POB1, through its influence on the Ral signalling pathway, is involved in growth factor signalling. Decreased expression of REPS2/POB1 during progression of prostate cancer may therefore result in loss of control of growth factor signalling and consequently in loss of control of cell proliferation.

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Author notes

  1. Leen J Blok: The nucleotide sequences reported in this paper have been submitted to GenBank under accession number AF511533 (REPS2a) and AF512951 (REPS2b)

  2. Leen J Blok: This work was supported by a grant from The Dutch Organisation for Scientific Research (reg.nr. 903-46-179)

Authors and Affiliations

  1. Department of Reproduction and Development, Erasmus MC, Erasmus University Rotterdam, PO Box 1738, Rotterdam, 3000, DR, The Netherlands

    Josien K Oosterhoff, Fred Penninkhof, Albert O Brinkmann & J Anton Grootegoed

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  1. Josien K Oosterhoff
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Oosterhoff, J., Penninkhof, F., Brinkmann, A. et al. REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells. Oncogene 22, 2920–2925 (2003). https://doi.org/10.1038/sj.onc.1206397

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