TY - JOUR
T1 - The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation
AU - Serafino, A.
AU - Balestrieri, E.
AU - Pierimarchi, P.
AU - Matteucci, C.
AU - Moroni, G.
AU - Oricchio, E.
AU - Rasi, G.
AU - Mastino, A.
AU - Spadafora, C.
AU - Garaci, E.
AU - Vallebona, P. Sinibaldi
PY - 2009/3/10
Y1 - 2009/3/10
N2 - Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.
AB - Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.
KW - Human endogenous retrovirus
KW - Human melanoma cells
KW - Malignant phenotype
KW - Melanoma progression
KW - Retroviral particle production
UR - http://www.scopus.com/inward/record.url?scp=59849108105&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59849108105&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2008.12.023
DO - 10.1016/j.yexcr.2008.12.023
M3 - Article
C2 - 19167380
AN - SCOPUS:59849108105
VL - 315
SP - 849
EP - 862
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 5
ER -