Expression of Fas and Fas-related molecules in human hepatocellular carcinoma

Citation
Sh. Lee et al., Expression of Fas and Fas-related molecules in human hepatocellular carcinoma, HUMAN PATH, 32(3), 2001, pp. 250-256
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Journal title
HUMAN PATHOLOGY
ISSN journal
0046-8177 → ACNP
Volume
32
Issue
3
Year of publication
2001
Pages
250 - 256
Database
ISI
SICI code
0046-8177(200103)32:3<250:EOFAFM>2.0.ZU;2-T
Abstract
Many tumor cells, including hepatocellular carcinoma (HCC), express both Fa s and its ligand on their surfaces, and it has remained a mystery why such cells do not spontaneously become apoptotic. In the current study, we analy zed the alterations of Fas structure and the expression of Fas and Fas liga nd (FasL) and of Fas pathway inhibitors, including soluble Fas (sFas), Fas- associated phosphatase-1 (FAP-1), and bcl-2, in 50 cases of human HCC. Mono allelic loss of the Fns gene, as determined by loss of heterozygosity with intragenic polymorphisms, was observed in 5 of the 34 informative cases (15 %), bur none of the 50 cases showed Fas gene mutation. Expression of Fas an d FasL was detected in 44 (88%) and 50 (100%) cases, respectively. sFas mes senger RNA, as analyzed by in situ reverse-transcription polymerase chain r eaction was expressed in 42 of the 50 cases (84%), and FAP-1 expression was observed in 40 of the 50 cases (80%). In contrast, none of the 50 cases sh owed bcl-2 expression. Our results showed that the majority of the HCCs (88 %) coexpressed a death receptor, Fas and its cognate ligand, FasL, but all HCCs showed one or more alterations of the Fas pathway molecules known to i nhibit Fas-mediated apoptosis. These findings suggest that the expression o f sFas and FAP-1 and, in part, loss of Fas expression, rather than Far gene alteration or bcl-2 expression, may be involved in the Fas resistance of H CC in vivo and that these mechanisms may play important roles in the pathog enesis of human HCC. HUM PATHOL 32: 250-256. Copyright (C) 2001 by W.B. Sau nders Company.