Expression of HERV-K correlates with status of MEK-ERK and p16INK4A-CDK4 pathways in melanoma cells.
The dysregulated ERK and RB pathways often coexist in melanoma cells. The K-type human endogenous retrovirus (HERV-K) is implicated in melanomagenesis. Some of the phenotypes that are modified by HERV-K (e.g., changes in cell shape, melanin production, and anchorage-dependent growth) overlap with those that are regulated by ERK and RB pathways. As ERK signaling can regulate retroviruses, we hypothesized that HERV-K expression is controlled by ERK-RB pathways. We found that the levels of HERV-K GAG and EVE correlated with the activation of ERK and loss of p16INK4A and that inhibition of MEK or CDK4, especially in combination, reduced HERV-K EVE in melanoma cells.
Li
Zhongwu
Z
Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555-0743, USA.
Sheng
Tao
T
Wan
Xiaohua
X
Liu
Tianshuang
T
Wu
Hai
H
Dong
Jianli
J
D015153:Blotting, Western; D045744:Cell Line, Tumor; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
D019941:Cyclin-Dependent Kinase Inhibitor p16; C406149:HERV-K cORF protein, Human endogenous retrovirus K; D014764:Viral Proteins; D051358:Cyclin-Dependent Kinase 4; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases