PTEN sensitizes epidermal growth factor-mediated proliferation in endometrial carcinoma cells.
The fact that the genetic alterations of PTEN are frequently found in hormone-dependent cancers, such as endometrial, breast, and prostate cancers, might suggest the involvement of PTEN in the hormone-dependent cell growth of such tumors. Estrogen promotes the cell growth of the tumors by inducing peptide growth factors in part. We analyzed the possible involvement of PTEN in peptide-growth factor-dependent cell growth in endometrial carcinoma cells. PTEN-null Ishikawa cells were efficiently infected with recombinant adenovirus at 20 MOI (multiplicity of infection) to express PTEN protein. In PTEN-IK cells, phospho-Akt/PKB was down-regulated regardless of the consistent expression of Akt/PKB. The cell growth of parental IK cells was significantly stimulated by EGF and IGF-I, and PTEN-IK cells were further sensitized to the EGF-or IGF-I-growth stimulation. EGFR antibody could completely compromise the stimulatory effects of EGF in both cell lines. Wortmannin, a PI3K inhibitor, or UO126, a MAPK inhibitor, partly suppressed EGF-mediated cell growth stimulation in both cell lines. EGF augmented the level of phospho-Akt/PKB of PTEN-IK cells more effectively than that of parental IK cells. These results imply that the dysfunction of PTEN leads cells into a less-sensitive phenotype to peptide growth factors by constitutive activation of the PI3K/Akt/PKB signaling pathway in endometrial carcinoma.
Tang
Liu Lin
LL
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Gifu 501-1194, Japan. tangliulin@hotmail.com
Yokoyama
Yasuhiro
Y
Wan
Xiaoyun
X
Iwagaki
Shigenori
S
Niwa
Kenji
K
Tamaya
Teruhiko
T
D000256:Adenoviridae / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004274:DNA, Recombinant / Q000235:genetics; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D000906:Antibodies; D002070:Butadienes; D004274:DNA, Recombinant; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D016222:Fibroblast Growth Factor 2; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles; D051059:PTEN Phosphohydrolase; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077191:Wortmannin; C066855:HGF protein, human; C113580:U 0126; C494929:PTEN protein, human