Analysis of APAF-1 expression in human cutaneous melanoma progression.
APAF-1 plays a pivotal role in mitochondria-dependent apoptosis, binding to cytochrome c and favoring activation of caspase-9. It has been shown that epigenetic silencing of the APAF-1 gene is a common event in several metastatic melanoma cells in vitro. We determined, by Western blot, variation in the level of expression of APAF-1 in several human melanoma cell lines and, by immunohistochemistry, in a group of 106 histological samples including benign and malignant melanocytic lesions. We observed APAF-1 down-regulation or loss of expression in two metastatic melanoma cell lines, compared to primary melanoma cell lines. The immunohistochemical analysis revealed a significant difference in APAF-1 staining between nevi and melanomas. In addition, we found a significant negative correlation between APAF-1 expression level and tumor thickness and between primary melanomas and metastases. We conclude that loss of APAF-1 expression can be considered as an indicator of malignant transformation in melanoma.
Baldi
Alfonso
A
Center for Experimental Research, Regina Elena Cancer Institute, Rome, Italy. alfonsobaldi@tiscali.it
Santini
Daniele
D
Russo
Patrizia
P
Catricalà
Caterina
C
Amantea
Ada
A
Picardo
Mauro
M
Tatangelo
Fabiana
F
Botti
Gerardo
G
Dragonetti
Emanuele
E
Murace
Raffaele
R
Tonini
Giuseppe
G
Natali
Pier Giorgio
PG
Baldi
Feliciano
F
Paggi
Marco G
MG
D017209:Apoptosis / Q000235:genetics; D053477:Apoptotic Protease-Activating Factor 1; D001706:Biopsy; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008928:Mitochondria / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins