Involvement of the c-Ski oncoprotein in cell cycle arrest and transformation during nurse cell formation after Trichinella spiralis infection.
The role of c-Ski, an oncoprotein encoded by the oncogene, c-ski, in Trichinella spiralis-infected muscle tissues during nurse cell formation, was investigated by following the expression kinetics and distribution of c-Ski (both protein and mRNA) in the infected muscle cell, as well as the expression kinetics of the transforming growth factor beta (TGF-beta) signaling pathway factor genes (TGF-beta, Smad2 and Smad4) which cooperate with c-Ski. Immunohistochemical analysis using an anti-c-Ski antibody indicated that in the early stages of infection (13 and 18 days post-infection (p.i.)) the increased expression of the c-Ski protein was limited to the eosinophilic cytoplasm and not the enlarged nuclei or basophilic cytoplasm. At a later stage of infection (23 and 28 days p.i.) the c-Ski protein was limited to the enlarged nuclei in the basophilic cytoplasm, rather than the eosinophilic cytoplasm. At 48 days p.i., the c-Ski protein was barely detectable. Real-time PCR analysis showed that expression of the c-ski gene increased from 13 days p.i., reached a peak at 23-28 days p.i. and then decreased to a low level by 48 days p.i. Expression kinetics for the TGF-beta signaling pathway factor genes (TGF-beta, Smad2 and Smad4) were similar to that of c-ski. These findings provide evidence that the c-Ski protein is involved in nurse cell formation through the TGF-beta signaling pathway process in the host cell nucleus.
Wu
Z
Z
Department of Parasitology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan.
Nagano
I
I
Boonmars
T
T
Takahashi
Y
Y
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007411:Intestinal Diseases, Parasitic / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D042282:Microdissection; D018613:Microscopy, Confocal; D023421:Models, Animal; D032342:Muscle Cells / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000378:metabolism* / Q000473:pathology
D015513:Oncogene Proteins; D051898:Smad1 Protein; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta