p8 inhibits the growth of human pancreatic cancer cells and its expression is induced through pathways involved in growth inhibition and repressed by factors promoting cell growth

被引：47

作者：

Cédric Malicet

Nathalie Lesavre

Sophie Vasseur

Juan L Iovanna

机构：

[1] Centre de Recherche INSERM, EMI 0116, 13288 Marseille Cedex

来源：

Molecular Cancer | / 2卷 / 1期

关键词：

JNK; p38; p8; Pancreatic cancer; Ras; TGFβ-1;

D O I：

10.1186/1476-4598-2-37

中图分类号：

学科分类号：

摘要：

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 downregulated 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. © 2003 Malicet et al; licensee BioMed Central Ltd.

引用

页数：12

共 33 条

[1] Mallo G.V., Fiedler F., Calvo E.L., Ortiz E.M., Vasseur S., Keim V., Morisset J., Iovanna J.L., Cloning and expression of the rat p8 cDNA, a new gene activated in pancreas during the acute phase of pancreatitis, pancreatic development, and regeneration, and which promotes cellular growth, J. Biol. Chem., 272, pp. 32360-32369, (1997)
[2] Jiang Y.F., Vaccaro M.I., Fiedler F., Calvo E.L., Iovanna J.L., Lipopolysaccharides induce p8 mRNA expression in vivo and in vitro, Biochem. Biophys. Res. Commun., 260, pp. 686-690, (1999)
[3] Garcia-Montero A., Vasseur S., Mallo G.V., Soubeyran P., Dagorn J.C., Iovanna J.L., Expression of the stress-induced p8 mRNA is transiently activated after culture medium change, Eur. J. Cell Biol., 80, pp. 720-725, (2001)
[4] Vasseur S., Mallo G.V., Fiedler F., Bodeker H., Canepa E., Moreno S., Iovanna J.L., Cloning and expression of the human p8, a nuclear protein with mitogenic activity, Eur. J. Biochem., 259, pp. 670-675, (1999)
[5] Vasseur S., Mallo G.V., Garcia-Montero A., Ortiz E.M., Fiedler F., Canepa E., Moreno S., Iovanna J.L., Structural and functional characterization of the mouse p8 gene: Promotion of transcription by the CAAT-enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta trans-acting factors involves a C/EBP cis-acting element and other regions of the promoter, Biochem. J., 343, pp. 377-383, (1999)
[6] Igarashi T., Kuroda H., Takahashi S., Asashima M., Cloning and characterization of the Xenopus laevis p8 gene, Develop Growth Differ., 43, pp. 693-698, (2001)
[7] Bustin M., Reeves R., High-mobility-group chromosomal proteins: Architectural components that facilitate chromatin function, Prog. Nucleic Acids Res. Mol. Biol., 54, pp. 35-100, (1996)
[8] Encinar J.A., Mallo G.V., Mizyrycki C., Giono L., Gonzalez-Ros J.M., Rico M., Canepa E., Moreno S., Neira J.L., Iovanna J.L., Human p8 is a HMG-I/Y-like protein with DNA binding activity enhanced by phosphorylation, J. Biol. Chem., 276, pp. 2742-2751, (2001)
[9] Hoffmeister A., Ropolo A., Vasseur S., Mallo G.V., Bodeker H., Ritz-Laser B., Dressler G.R., Vaccaro M.I., Dagorn J.C., Moreno S., Iovanna J.L., The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter, J. Biol. Chem., 277, pp. 22314-22319, (2002)
[10] Garcia-Montero A.C., Vasseur S., Giono L.E., Canepa E., Moreno S., Dagorn J.C., Iovanna J.L., Transforming growth factor beta-1 enhances Smad transcriptional activity through activation of p8 gene expression, Biochem. J., 357, pp. 249-253, (2001)

← 1 2 3 4 →