[HTML][HTML] p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors …

C Malicet, N Lesavre, S Vasseur, JL Iovanna - Molecular cancer, 2003 - Springer
C Malicet, N Lesavre, S Vasseur, JL Iovanna
Molecular cancer, 2003Springer
Background p8 is a stress-induced protein with multiple functions and biochemically related
to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in
pancreatic cancer-derived cells. Methods Expression of p8 was silenced in the human
pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8
RNA in the antisense orientation. Cell growth was measured in control and p8-silenced
cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular …
Background
p8 is a stress-induced protein with multiple functions and biochemically related to the architectural factor HMG-I/Y. We analyzed the expression and function of p8 in pancreatic cancer-derived cells.
Methods
Expression of p8 was silenced in the human pancreatic cancer cell lines Panc-1 and BxPc-3 by infection with a retrovirus expressing p8 RNA in the antisense orientation. Cell growth was measured in control and p8-silenced cells. Influence on p8 expression of the induction of intracellular pathways promoting cellular growth or growth arrest was monitored.
Results
p8-silenced cells grew more rapidly than control cells transfected with the empty retrovirus. Activation of the Ras→Raf→MEK→ERK and JNK intracellular pathways down-regulated p8 expression. In addition, the MEK1/2 inhibitor U0126 and the JNK inhibitor SP600125 up-regulates expression of p8. Conversely, p38 or TGFβ-1 induced p8 expression whereas the specific p38 inhibitor SB203580 down-regulated p8 expression. Finally, TGFβ-1 induction was in part mediated through p38.
Conclusions
p8 inhibits the growth of human pancreatic cancer cells. p8 expression is induced through pathways involved in growth inhibition and repressed by factors that promote cell growth. These results suggest that p8 belongs to a pathway regulating the growth of pancreatic cancer cells.
Springer