REPS2/POB1 is downregulated during human prostate cancer progression and inhibits growth factor signalling in prostate cancer cells.
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 NH(2)-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.
Oosterhoff
Josien K
JK
Department of Reproduction and Development, Erasmus MC, Erasmus University Rotterdam, PO Box 1738, 3000 DR, Rotterdam, The Netherlands.
Penninkhof
Fred
F
Brinkmann
Albert O
AO
Anton Grootegoed
J
J
Blok
Leen J
LJ
D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015723:Gene Library; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D006133:Growth Substances; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; C489722:REPS2 protein, human; D012333:RNA, Messenger