Reversal of the malignant phenotype of ovarian cancer A2780 cells through transfection with wild-type PTEN gene.
OBJECTIVE
PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor gene identified on human chromosome 10q23. Substantial studies have demonstrated that PTEN can inhibit cell proliferation, migration and invasion of many cancer cells. The purpose of this study was to determine whether upregulation of PTEN gene by transfection wild-type PTEN gene to ovarian cancer cells can inhibit growth and migration and to explore the potential for PTEN gene therapy of ovarian cancers.


METHODS
Wild-type and phosphatase-inactive (C124A) PTEN plasmids were transfected into ovarian epithelial cancer A2780 cells, and their effects on cell apoptosis, cell proliferation, cell migration and cell invasion were analyzed by flow cytometry analysis, TUNEL assay, MTT assay, wound-healing assay and transwell assay.


RESULTS
Both wild-type and mutant PTEN can upregulate the expression of PTEN gene dramatically; however, it is wild-type PTEN not phosphatase-inactive PTEN that can induce apoptosis and decrease cell migration, invasion and proliferation in ovarian cancer cells.


CONCLUSIONS
These results demonstrated that PTEN had played an important role in the cell proliferation, cell migration and invasion dependent on its phosphatase activity. Enhanced expression of PTEN by gene transfer is sufficient to reverse the malignant phenotype of ovarian cancer cells and transfection of ovarian cancer cells with wild-type PTEN gene might be another novel approach for therapeutic intervention in ovarian cancer.
Wu
Huijuan
H
Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
Wang
Shixuan
S
Weng
Danghui
D
Xing
Hui
H
Song
Xiaohong
X
Zhu
Tao
T
Xia
Xi
X
Weng
Yanjie
Y
Xu
Gang
G
Meng
Li
L
Zhou
Jianfeng
J
Ma
Ding
D
D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010641:Phenotype; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D017931:DNA Primers; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human