Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma.
Human pituitary tumour-transforming gene 1 or hPTTG1 is a proto-oncogene that codes for securin, a protein involved in sister chromatid separation. Based on previous microarray data, we studied the expression of hPTTG1/securin in melanocytic lesions. In contrast to nevi and radial growth phase melanomas, securin was expressed by scattered cells in the vertical growth phase, suggesting a role in tumour progression. In a series of 29 nodular and 29 superficial spreading melanomas, matched for all histological prognostic parameters, securin expression was significantly correlated with the nodular subtype (P=0.018) and not related to thickness. In other cancers, hPTTG1 is involved in various oncogenic pathways, including induction of neovascularisation and aneuploidy, and inhibition of p53 activity. We found coexpression of securin with wild-type p53 in the same neoplastic cells in a minority of melanomas. Expression of securin was significantly correlated with the extent of aneuploidy but not with basic fibroblast growth factor immunoreactivity or microvessel density. DNA cytometry revealed that nuclei-overexpressing securin frequently showed tetraploidy or aneuploidy. Our data show that hPTTG1 is frequently overexpressed in nodular melanoma, and suggest that hPTTG1 may act as an oncogene in the vertical growth phase, either by inhibiting anaphase, thereby causing aneuploidy and genomic instability, or by modulating the function of p53, thereby impairing apoptosis.
Winnepenninckx
Véronique
V
Department of Morphology and Molecular Pathology, University Hospitals, Katholieke Universiteit Leuven (KUL), Leuven, Belgium.
Debiec-Rychter
Maria
M
Beliën
Jeroen A M
JA
Fiten
Pierre
P
Michiels
Stefan
S
Lazar
Vladimir
V
Opdenakker
Ghislain
G
Meijer
Gerrit A
GA
Spatz
Alain
A
van den Oord
Joost J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009506:Nevus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D064249:Securin; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D064249:Securin; D016159:Tumor Suppressor Protein p53; C578002:pituitary tumor-transforming protein 1, human; D016222:Fibroblast Growth Factor 2