Fas death pathway in sarcomas correlates with epidermal growth factor transcription.
Modulation of apoptosis may influence sarcoma pathogenesis and/or aggressiveness. The Fas death pathway, mediated by FasL or TGFbeta, is one of two apoptotic pathways. Recent studies report that EGF can modulate TGFbeta and/or FasL expression/activity; thus, EGF has the potential to influence activation of the Fas pathway. EGF is not always detectable in mesenchymal tumors; therefore, we hypothesized EGF would define which Fas ligand predominates. We assayed 57 surgically removed human sarcomas for 10 genes involved in the Fas pathway. Skeletal muscle biopsies from eight patients served as controls. Sample transcripts were detected by real-time RT-PCR. We attempted to identify relevant predictor variables. The 57 sarcomas were segregated into two categories defined by EGF mRNA content: (1) 23 tumors with EGF concentrations that approximated muscle EGF transcript levels (high-EGF tumors); and (2) 34 tumors that either lacked EGF mRNA, or whose mRNA levels were very low and frequently undetected by PCR (low-EGF tumors). TGFbeta1 expression best predicted Fas transcript concentrations in the 34 low-EGF sarcomas, while FasL predicted Fas mRNA levels in the remaining 23 high-EGF sarcomas. The results suggest ligand activity in the Fas death pathway correlates with EGF transcription in sarcomas.
Joyner
David E
DE
Department of Orthopaedics, Sarcoma Services, Huntsman Cancer Institute, University of Utah School of Medicine, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Aboulafia
Albert J
AJ
Damron
Timothy A
TA
Randall
R Lor
RL
D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D053455:Caspase 10 / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics*; D053222:Fas Ligand Protein / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D018482:Muscle, Skeletal / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D012044:Regression Analysis; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D053418:Death Domain Receptor Signaling Adaptor Proteins; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D053455:Caspase 10; D053181:Caspase 8