Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.
The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.
Lilja
J F
JF
Department of Obstetrics and Gynecology, The University of Michigan Comprehensive Cancer Center, Ann Arbor 48109, USA.
Wu
D
D
Reynolds
R K
RK
Lin
J
J
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051381:Rats; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; C494918:AKT1 protein, human; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human