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. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 126 (8). pp. 1850-1859. ISSN 0022-202X,
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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-homolog1 (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 (TM) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MALIGNANT-MELANOMA; GENE-PRODUCT; EXPRESSION; TRANSCRIPTION; GROWTH; CYCLE; PHOSPHORYLATION; PROGRESSION; TARGET; INVOLVEMENT; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Biology, Preclinical Medicine > Institut für Biochemie, Genetik und Mikrobiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Feb 2021 07:39 |
| Last Modified: | 09 Feb 2021 07:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34243 |
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