Publication: Molecular changes in human melanoma metastasis
Authors
Luca, M.R. ; Bar-Eli, M.
item.page.secondaryauthor
item.page.director
Publisher
Murcia : F. Hernández
publication.page.editor
publication.page.department
DOI
item.page.type
info:eu-repo/semantics/article
Description
Abstract
The molecular changes associated with the
transition of melanoma cells from radial growth phase to
vertical growth phase (metastatic phenotype) are not
well defined. Our recent studies have demonstrated that
the two tumor suppressor genes, p53 and p16/CDKN2,
do not play a major role in the acquisition of the
metastatic phenotype in human melanoma. Mutations in
p53 are infrequent and do not correlate with the
metastatic potential of human melanoma cells while
p161CDKN2 abnormalities are frequent, but are not prerequisite
for the acquistion of the metastatic phenotype.
On the other hand, the tyrosine-kinase receptor c-KIT
and the cell adhesion molecule MCAMIMUC-18 play
active roles in the progression of human melanoma.
Metastatic melanoma cells overexpress MCAM and do
not express the c-KIT receptor. Enforced c-KIT
expression in metastatic cells significantly inhibited their
growth and metastatic potential in nude mice.
Furthermore, exposure of c-KIT-positive melanoma cells
in vitro and in vivo to stem cell factor (SCF), the ligand
for c-KIT, triggered apoptosis of these cells but not of
normal melanocytes. Ectopic expression of MCAM into
primary cutaneous melanoma cells enhanced their
tumorigenicity and met$static ability in vivo. We found
that both genes, c-KIT and MCAM, are regulated by the
transcription factor AP-2 and that metastatic melanoma
cells do not express AP-2. We therefore propose that loss
of AP-2 might be a crucial event in the progression of
human melanoma.
publication.page.subject
Citation
item.page.embargo
Ir a Estadísticas
Sin licencia Creative Commons.