MCL-1, BCL-XL and MITF Are Diversely Employed in Adaptive Response of Melanoma Cells to Changes in Microenvironment.

摘要: Melanoma cells can switch their phenotypes in response to microenvironmental insults. Heterogeneous melanoma populations characterized by long-term growth and a high self-renewal capacity be obtained vitro EGF(+)bFGF(+) medium whilst invasive potential of is increased serum-containing cultures. In the present study, we have shown that originally these patient-derived exhibit variable expression pro-survival genes from BCL-2 family inhibitors apoptosis (IAPs), differ baseline MCL-1 transcript stability as well. While being transferred medium, are well protected death. Immediate adaptive selectively involves temporary increase, both at mRNA protein levels, BCL-XL complement MCL-1, especially MITFlow populations. Thus, extent contributions seems cell context-dependent. An increase level results transiently enhanced its transcript, but not altered turnover. Inhibition preceding transfer caused induction death subset cells, which confirms involvement survival during rapid alteration conditions. Additionally, immediate serum transient MITF inhibition ERK-1/2 activity. Uncovering mechanisms changes microenvironment may extend our knowledge on biology, stage dissemination.