Roesch, Alexander and Becker, Bernd and Schneider-Brachert, Wulf and Hagen, Ilja and Landthaler, Michael and Vogt, Thomas (2006) Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells. The Journal of investigative dermatology 126 (8), pp. 1850-1859.
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Other URL: http://dx.doi.org/10.1038/sj.jid.5700324
The loss of cell cycle control in malignant melanomas is thought to be due to a lack of retinoblastoma protein (pRb) activity. We have recently reported a progressive deficiency of the retinoblastoma-binding protein 2-homolog 1 (RBP2-H1) in advanced and metastatic melanomas in vivo, suggesting a role of RBP2-H1 in loss of pRb-mediated control. Therefore, in this study, we re-established the pRb-modulating function of RBP2-H1 in highly metastatic A375-SM melanoma cells by re-expressing its C-term (cRBP2-H1). As previously shown, the corresponding domains comprise the pRb-binding region of the RBP2-H1 protein (non-T/E1A-pRb-binding domain (NTE1A)). As a result, we detected pRb-hypophosphorylation selectively at Ser795, but not at Ser780 and Ser807/811 throughout the G1 phase of the cell cycle. As a further consequence, a block in G1/S transition was observed accompanied by a significant decrease of DNA replication and cellular proliferation. As demonstrated by cDNA microarrays of cRBP2-H1-transduced cells and confirmed by quantitative TaqMan reverse transcriptase-PCR, differential expression of melanoma-progression-related genes was observed, among them bone morphogenetic protein 2, follistatin, transforming growth factor alpha, hepatocyte growth factor, transcription factor 4 and microphthalmia-associated transcription factor. Conclusively, these data suggest that RBP2-H1 exerts a broad tumor-suppressive function partially mediated by pRb modulation. Therefore, re-establishing of RBP2-H1 could evolve as an interesting novel approach in developing experimental treatments for metastatic melanomas.
|Institutions:||Medicine > Lehrstuhl für Dermatologie und Venerologie|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||30 Mar 2007|
|Last Modified:||20 Jul 2011 21:05|