Mitogen-actived protein kinase activation is an early event in melanoma progression.
OBJECTIVE
Melanoma is the most common cause of death from cutaneous malignancy, and is the cancer that is most rapidly rising in incidence. Because current therapeutic methods for metastatic melanoma are poorly efficacious, enhanced understanding of signal transduction in melanoma progression is warranted. Prior experimental studies in murine models and human tissues have shown a correlation among activation of mitogen activated protein kinase (MAPK) signaling, angiogenesis, and tumorigenesis. Because of these findings, we wanted to assess the role of MAPK signaling in melanoma progression and angiogenesis.


METHODS
We studied expression of phosphorylated (active) MAPK and two target genes known to be induced by MAPK signaling, tissue factor and vascular endothelial growth factor, in 131 melanocytic lesions, ranging from atypical nevi to metastatic melanoma.


RESULTS
We observed little staining for activated (phosphorylated) MAPK and low amounts of angiogenesis in atypical nevi, but angiogenesis and MAPK activation were activated in radial growth melanoma and in later stage lesions.


CONCLUSIONS
Our findings implicate MAPK activation as an early event in melanoma progression, and MAPK may be a potential target for pharmacologic intervention.
Cohen
Cynthia
C
Department of Pathology, Public Health, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Zavala-Pompa
Angel
A
Sequeira
Judy H
JH
Shoji
Mamoru
M
Sexton
Deborah G
DG
Cotsonis
George
G
Cerimele
Francesca
F
Govindarajan
Baskaran
B
Macaron
Nada
N
Arbiser
Jack L
JL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009508:Nevus, Pigmented / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D013925:Thromboplastin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A
D043925:Angiogenesis Inducing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013925:Thromboplastin; D020928:Mitogen-Activated Protein Kinases