Inverse correlation between p16INK4A expression and NF-kappaB activation in melanoma progression.
Expression of p16INK4A, the product of the melanoma susceptibility gene CDKN2A, has been shown to decrease in correlation with tumor progression. P16INK4A is a key regulator of cell-cycle function, and likely interacts with a variety of targets alongside cyclin-dependent kinases (CDKs). One such target is nuclear factor KB (NF-kappaB), a pleiotropic transcription factor that plays a crucial role in apoptosis, oncogenesis and cell cycle control. NF-kappaB p65 has been shown to be activated in melanoma cell lines but few studies decribe its expression in the tissue. In the present study we focused on synchronous expression of p16INK4A and NF-kappaB p65 and their functional activation in melanoma cell lines and biopsy tissue. Activation of NF-kappaB p65, as observed by electrophoretic mobility shift assay in cell lines, was correlated with expression and cellular localization of the active and inactive forms of its inhibitor, IkappaB-alpha. In melanocytic lesions, p16INK4A and NF-kappaB p65 expression were inversely correlated with levels of the nuclear component of NF-kappaB p65 increasing from nevi to primary melanomas and metastases.
Department of Oncology, Biology and Genetics, University of Genova, Italy.
Paola
P
Ghiorzo
Michela
M
Mantelli
Sara
S
Gargiulo
Claudia
C
Gramigni
Lorenza
L
Pastorino
Barbara
B
Banelli
Barbara
B
Villaggio
Maria Cristina
MC
Coccia
Angela Rita
AR
Sementa
Cecilia
C
Garrè
Giovanna
G
Bianchi-Scarrà
D045744:Cell Line, Tumor / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000556:secondary; D016328:NF-kappa B / Q000096:biosynthesis*; D009506:Nevus / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D016328:NF-kappa B