Mitogen-actived protein kinase activation is an early event in melanoma progression

C Cohen, A Zavala-Pompa, JH Sequeira, M Shoji… - Clinical cancer …, 2002 - AACR
C Cohen, A Zavala-Pompa, JH Sequeira, M Shoji, DG Sexton, G Cotsonis, F Cerimele…
Clinical cancer research, 2002AACR
Purpose: 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 …
Abstract
Purpose: 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.
Experimental Design: 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.
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