title: Evidence for differential expression of Notch receptors and their ligands in melanocytic nevi and cutaneous malignant melanoma.
abstract: The Notch signaling has been implicated in the regulation of self-renewal of adult stem cells and differentiation of precursors along a specific cell lineage, in normal embryonic development and organogenesis. There is also evidence that signaling through Notch receptors regulate cell proliferation and cell survival in several types of cancer, with opposing results depending on tissue context. No data are available in the literature concerning modulation of the expression of Notch receptors, and their ligands, in human cutaneous malignant melanoma. Here, we have investigated, for the first time, the expression of Notch-1, Notch-2, Jagged-1, Jagged-2 and Delta-like 1 proteins, by immunohistochemistry, in a series of benign and malignant human melanocytic lesions: five common melanocytic nevi, five 'dysplastic nevi' and 20 melanomas (five in situ, five T1-T2, five T3-T4 and five metastatic melanomas). We found that the expression of Notch-1 and Notch-2, as well as Notch ligands, was upregulated in 'dysplastic nevi' and melanomas as compared with common melanocytic nevi. These results indicate that the activation of Notch may represent an early event in melanocytic tumor growth and upregulation of Notch signaling may sustain tumor progression.
authors.affiliation: Department of Human Pathology and Oncology, University of Florence, Florence, Italy. Daniela.massi@UNIFI.IT
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Francesca
authors.initials: F
authors.lastname: Tarantini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Franchi
authors.forename: Milena
authors.initials: M
authors.lastname: Paglierani
authors.forename: Claudia
authors.initials: C
authors.lastname: Di Serio
authors.forename: Silvia
authors.initials: S
authors.lastname: Pellerito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Leoncini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins / Q000032:analysis; D004817:Epidermis / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D015603:Keratinocytes / Q000737:chemistry / Q000473:pathology; D008024:Ligands; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins / Q000032:analysis; D008875:Middle Aged; D009508:Nevus, Pigmented / Q000378:metabolism / Q000473:pathology*; D051881:Receptor, Notch1 / Q000032:analysis; D051883:Receptor, Notch2 / Q000032:analysis; D051880:Receptors, Notch / Q000032:analysis*; D000072099:Serrate-Jagged Proteins; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C490504:JAG2 protein, human; D000072100:Jagged-1 Protein; D000072101:Jagged-2 Protein; D008024:Ligands; D008565:Membrane Proteins; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C064045:delta protein