Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma.
The tumor suppressor PTEN acts as a lipid phosphatase, regulates the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway, and modulates cell cycle progression and cell survival. Somatic mutations of PTEN have been reported in a variety of cancers, especially in endometrial carcinoma. To clarify whether and how PTEN and the PI3K/Akt pathway relates to endometrial carcinoma, we examined the expression of those pathway-related proteins in patients with endometrial carcinoma. Of 103 endometrial carcinomas, 37 (36%) showed negative immunohistochemical staining of PTEN. Western blotting revealed that the expression of PTEN in PTEN-negative cases was significantly lower compared with that in positive cases. In contrast, phospho-Akt level in negative cases was significantly higher. We found a significant inverse correlation between PTEN and phospho-Akt (r = -0.796). The expression of phospho-Bad was greater in negative cases, suggesting that Bad might be a target for AKT: The present study demonstrates the phosphorylation of Akt accompanied by the loss of PTEN in clinical specimens of endometrial carcinomas.
Kanamori
Y
Y
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago 683-8504, Japan. kanamori@grape.med.tottori-u.ac.jp
Kigawa
J
J
Itamochi
H
H
Shimada
M
M
Takahashi
M
M
Kamazawa
S
S
Sato
S
S
Akeshima
R
R
Terakawa
N
N
D002352:Carrier Proteins / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013223:Statistics as Topic; D025521:Tumor Suppressor Proteins; D051025:bcl-Associated Death Protein
D002352:Carrier Proteins; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D025521:Tumor Suppressor Proteins; D051025:bcl-Associated Death Protein; C494819:BAD protein, human; C494918:AKT1 protein, human; C494929:PTEN protein, human