Journal Article DKFZ-2018-02302

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Targeted Therapy-Resistant Melanoma Cells Acquire Transcriptomic Similarities with Human Melanoblasts.

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2018
MDPI Basel

Cancers 10(11), 451 () [10.3390/cancers10110451]
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Abstract: The mechanisms of adaptive and acquired drug resistance in tumors are not completely understood. So far, gene amplifications or mutations, leading to the reactivation of the MAPK or PI3K pathways have been described. In this study, we used two different methods to generate human melanoblasts: (1) via differentiation from induced pluripotent stem cells (iPSCs) and (2) via dedifferentiation from melanocytes. The melanoblast transcriptomes were then compared to the transcriptome of MAPK inhibitor-resistant melanoma cells. We observed that the expression of genes associated with cell cycle control, DNA damage control, metabolism, and cancer was altered in both melanoblast populations and in both adaptive and acquired resistant melanoma samples, compared to drug-sensitive samples. However, genes involved in antigen presentation and cellular movement were only regulated in the melanoblast populations and in the acquired resistant melanoma samples, compared to the drug-sensitive samples. Moreover, melanocyte-derived melanoblasts and adaptive resistant melanoma samples were characterized by different expression levels of certain transcription factors or genes involved in the CDK5 pathway. In conclusion, we show here that in vitro models of human melanoblasts are very important tools to comprehend the expression profiles of drug-resistant melanoma.

Classification:

Contributing Institute(s):
  1. KKE Dermatoonkologie (G300)
  2. KKE Nuklearmedizin (E060)
Research Program(s):
  1. 317 - Translational cancer research (POF3-317) (POF3-317)

Appears in the scientific report 2018
Database coverage:
Medline ; Creative Commons Attribution CC BY (No Version) ; DOAJ ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2018-12-29, last modified 2024-02-29


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