PTEN deletion leads to up-regulation of a secreted growth factor pleiotrophin.
Tumor suppressor gene PTEN is highly mutated in a wide variety of human tumors. To identify unknown targets or signal transduction pathways that are regulated by PTEN, microarray analysis was performed to compare the gene expression profiles of Pten null mouse embryonic fibroblasts (MEFs) cell lines and their isogenic counterparts. Expression of a heparin binding growth factor, pleiotrophin (Ptn), was found to be up-regulated in Pten-/- MEFs as well as Pten null mammary tumors. Further experiments revealed that Ptn expression is regulated by the PTEN-PI3K-AKT pathway. Knocking down the expression of Ptn by small interfering RNA resulted in the reduction of Akt and GSK-3beta phosphorylation and suppression of the growth and the tumorigenicity of Pten null MEFs. Our results suggest that PTN participates in tumorigenesis caused by PTEN loss and PTN may be a potential target for anticancer therapy, especially for those tumors with PTEN deficiencies.
Li
Gang
G
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-1735, USA. ligang@nic.bmi.ac.cn
Hu
Yingchun
Y
Huo
Yanying
Y
Liu
Minli
M
Freeman
Dan
D
Gao
Jing
J
Liu
Xin
X
Wu
De-Chang
DC
Wu
Hong
H
D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D015233:Models, Statistical; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010766:Phosphorylation; D012313:RNA / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D002352:Carrier Proteins; D016207:Cytokines; D034741:RNA, Small Interfering; C066845:pleiotrophin; D012313:RNA; D051059:PTEN Phosphohydrolase; D000111:Acetylcysteine