Role of ROC1 protein in the control of cyclin D1 protein expression in skin melanomas
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Updated: Jun 4, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
Gisele Nai1, Mariângela Marques
1Department of Pathology, Botucatu Medical School, São Paulo State University (UNESP), Brazil. patologia@unoeste.br
Abstract:
A decrease in the level of the ROC1 protein, which is involved in cyclin D1 degradation, might explain an increase in cyclin D1 protein in the absence of gene overexpression. This study aimed to investigate the relationship between ROC1 and cyclin D1 expression in skin melanomas. A total of 62 cases of primary skin melanomas and 58 cases of compound melanocytic nevi were assessed. Immunohistochemistry was performed using cyclin D1 and ROC1 antibodies, and fluorescent in situ hybridization was used to assess the amplification of the CCND1 gene. ROC1 was expressed in >50% of cells in 87.9% of the melanocytic nevus cases and in 45.2% of the melanoma cases (p=0.0014). There was a significant negative correlation between ROC1 and cyclin D1 expression in all cases (p=0.0008985). In comparison with cyclin D1, ROC1 expression was increased in 86.2% of the melanocytic nevi and in 45.2% of the melanomas (p<0.001). Among the non-amplified melanomas, 50% expressed cyclin D1 in >50% of the cells and expressed ROC1 in <25%. ROC1 expression is negatively correlated with cyclin D1 expression, demonstrating its importance in the degradation of cyclin D1 in melanomas.
Insights
ROC1 protein levels decrease in melanoma, leading to increased cyclin D1. This study highlights ROC1
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Cyclin D1 is crucial for cell cycle progression.
- ROC1 (Regulator of Cullins 1) is implicated in cyclin D1 degradation.
- Altered expression of these proteins may contribute to melanoma development.
Purpose of the Study:
- To investigate the relationship between ROC1 and cyclin D1 expression in skin melanomas.
- To determine if ROC1 levels correlate with cyclin D1 levels in melanoma and melanocytic nevi.
Main Methods:
- Immunohistochemistry was used to assess ROC1 and cyclin D1 protein expression in 62 melanomas and 58 nevi.
- Fluorescent in situ hybridization (FISH) was employed to detect CCND1 gene amplification.
Main Results:
- ROC1 expression was significantly lower in melanomas (45.2%) compared to melanocytic nevi (87.9%).
- A significant negative correlation was observed between ROC1 and cyclin D1 expression in all samples.
- In non-amplified melanomas, reduced ROC1 correlated with increased cyclin D1 expression.
Conclusions:
- ROC1 plays a role in regulating cyclin D1 levels in melanoma.
- Decreased ROC1 expression contributes to elevated cyclin D1 in melanoma, independent of gene amplification.
- ROC1's function in cyclin D1 degradation is critical in melanoma pathogenesis.
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