Gene Expression Signature of BRAF Inhibitor Resistant Melanoma Spheroids.

Gene Expression Signature of BRAF Inhibitor Resistant Melanoma Spheroids.
Pathol Oncol Res. 2020 Jul 01;:
Authors: Koroknai V, Patel V, Szász I, Ádány R, Balazs M
Abstract
In vitro cell cultures are frequently used to define the molecular background of drug resistance. The majority of currently available data have been obtained from 2D in vitro cultures, however, 3D cell culture systems (spheroids) are more likely to behave similarly to in vivo conditions. Our major aim was to compare the gene expression signature of 2D and 3D cultured BRAFV600E mutant melanoma cell lines. We successfully developed BRAF-drug resistant cell lines from paired primary/metastatic melanoma cell lines in both 2D and 3D in vitro cultures. Using Affymetrix Human Gene 1.0 ST arrays, we determined the gene expression pattern of all cell lines. Our analysis revealed 1049 genes (562 upregulated and 487 downregulated) that were differentially expressed between drug-sensitive cells grown under different cell cultures. Pathway analysis showed that the differently expressed genes were mainly associated with the cell cycle, p53, and other cancer-related pathways. The number of upregulated genes (72 genes) was remarkably fewer when comparing the resistant adherent cells to cells that grow in 3D, and were associated with cell adhesion molecules and IGF1R signalling. Only 1% of the upregulated and 5.6% of the downregulated genes were commonly altered between the sens...

Source: Pathology Oncology Research - June 30, 2020 Category: Pathology Authors: Koroknai V, Patel V, Szász I, Ádány R, Balazs M Tags: Pathol Oncol Res Source Type: research