Suppression of cell migration in ovarian cancer cells mediated by PTEN overexpression.
Peritoneal dissemination is the major progression pathway of ovarian cancer, and its control is important for improvement of the prognosis. PTEN is a tumor suppressor gene, and is known to inhibit cancer cell growth and migration. To investigate the possibility of gene therapy using PTEN for ovarian cancer, we introduced PTEN cDNA into an ovarian cancer cell line HRA carrying wild-type PTEN, and examined the effects in vitro and in vivo. Using PTEN cDNA cloned from a human liver cDNA library, a PTEN expression vector was constructed. This vector was introduced into HRA cells by the standard calcium phosphate precipitation method, and an HRA cell line overexpressing PTEN (HRA/PTEN) was established. On the cell migration test by in vitro scratch wound healing assay, the number of migrating cells was 6.3+/-0.9 cells/mm(2) in HRA/PTEN, which was significantly smaller than that in the control (39.7+/-3.2 cells/mm(2)) (p<0.01). No significant differences were observed in the in vitro cell growth or in vivo tumor growth between HRA/PTEN and the control. The findings described above, show that enhanced expression of PTEN inhibits ovarian cancer cell migration, suggesting that gene therapy approaches using PTEN for control of peritoneal dissemination of ovarian cancer are possible.
Saga
Yasushi
Y
Department of Obstetrics and Gynecology, Jichi Medical School, Yakushiji, Minamikawachi Tochigi 329-0498, Japan. saga@jichi.ac.jp
Mizukami
Hiroaki
H
Takei
Yuji
Y
Ozawa
Keiya
K
Suzuki
Mitsuaki
M
D000818:Animals; D015153:Blotting, Western; D002130:Calcium Phosphates / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011379:Prognosis; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*; D014443:Tyrosine / Q000378:metabolism; D014945:Wound Healing
D002130:Calcium Phosphates; D018076:DNA, Complementary; D025521:Tumor Suppressor Proteins; D014443:Tyrosine; C020243:calcium phosphate; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human