Influence of melanoma inhibitory activity on transforming growth factor-beta signaling in malignant melanoma

Rothhammer, Tanja and Bosserhoff, Anja-Katrin (2006) Influence of melanoma inhibitory activity on transforming growth factor-beta signaling in malignant melanoma. MELANOMA RESEARCH, 16 (4). pp. 309-316. ISSN 0960-8931,

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Abstract

Melanoma cells escape transforming growth factor-P (TGF beta)-mediated growth inhibition by expressing the Smad (mothers against decapentaplegic homolog, Drosophila) inhibitors Ski and Sno. Here, we demonstrate that melanoma inhibitory activity (MIA) influences the expression of these inhibitors. A Smad responsive reporter construct was activated after TGF beta 1 treatment in the MIA-deficient cell clones but not in the parental cell line. According to this finding, the TGF beta target genes JunB and Id-1 showed a strong induction of expression. Additional analyses revealed that Ski and Sno, repressors of TGF beta/ SMAD signaling, are not expressed in the MIA-deficient cells but in the parental cell line HMB2 and the mock control. Further investigation showed that Ski and Sno expression might be regulated via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling cascade. Treatment of HMB2 cells with a MEK inhibitor revealed a reduction of Ski and Sno expression, which leads to the conclusion that, in our melanoma cell model, Ski and Sno expression is regulated via MAPK/ERK signaling.

Item Type: Article
Uncontrolled Keywords: ONCOGENIC PROTEIN SKI; MIA; EXPRESSION; CELLS; PROGRESSION; CANCER; MAPK/ERK; melanoma inhibitory activity; Ski; Sno; transforming growth factor-beta signaling
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Feb 2021 11:44
Last Modified: 09 Feb 2021 11:44
URI: https://pred.uni-regensburg.de/id/eprint/34251

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