title: MCL-1, BCL-XL and MITF Are Diversely Employed in Adaptive Response of Melanoma Cells to Changes in Microenvironment.
abstract: 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 can be obtained in vitro in EGF(+)bFGF(+) medium whilst invasive potential of melanoma cells is increased in serum-containing cultures. In the present study, we have shown that originally these patient-derived melanoma populations exhibit variable expression of pro-survival genes from the BCL-2 family and inhibitors of apoptosis (IAPs), and differ in the baseline MCL-1 transcript stability as well. While being transferred to serum-containing medium, melanoma cells are well protected from death. Immediate adaptive response of melanoma cells selectively involves a temporary MCL-1 increase, both at mRNA and protein levels, and BCL-XL can complement MCL-1, especially in MITFlow populations. Thus, the extent of MCL-1 and BCL-XL contributions seems to be cell context-dependent. An increase in MCL-1 level results from a transiently enhanced stability of its transcript, but not from altered protein turnover. Inhibition of MCL-1 preceding transfer to serum-containing medium caused the induction of cell death in a subset of melanoma cells, which confirms the involvement of MCL-1 in melanoma cell survival during the rapid alteration of growth conditions. Additionally, immediate response to serum involves the transient increase in MITF expression and inhibition of ERK-1/2 activity. Uncovering the mechanisms of adaptive response to rapid changes in microenvironment may extend our knowledge on melanoma biology, especially at the stage of dissemination.
authors.affiliation: Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
authors.forename: Mariusz L
authors.initials: ML
authors.lastname: Hartman
authors.affiliation: Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Talar
authors.affiliation: Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Gajos-Michniewicz
authors.affiliation: Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czyz
mesh_terms: D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494811:BCL2L1 protein, human; C579095:MCL1 protein, human; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D012333:RNA, Messenger; D051020:bcl-X Protein