Overexpression of p27(Kip1) induces growth arrest and apoptosis in an oral cancer cell line.
p27(Kip1) is a cyclin-dependent kinase inhibitor which regulates progression of cells from G1 into S phase in a cell cycle. Loss of p27(Kip1) has been associated with disease progression and an unfavorable outcome in several malignancies. In the present study, we conducted to examine whether up-regulation or down-regulation of p27(KiP1) can affect the growth of oral cancer cell (B88 cell) in vitro and in vivo. We constructed an expression vector containing sense- or antisense-oriented human p27(Kip1) cDNA with pcDNA3.1(Invitrogen). We transfected B88 cells with the sense or antisense expression vector to regulate the expression of p27(Kip1) gene in each transfectant. The expression of p27(Kip1) protein was up-regulated in the sense transfectants and down-regulated in the antisense transfectants. Moreover, up-regulation of p27(Kip1) protein exerted the growth inhibitory effect, and down-regulation of p27(Kip1) protein enhanced the growth of B88 cells in vitro and in vivo. Furthermore, we detected the G1 arrest and sub-G1 peak in the sense transfectants by flow cytometry analysis. These results suggest that up-regulation of p27(Kip1) protein may exert the growth inhibitory effects through induction of G1 arrest and apoptosis on oral cancer cell line.
Supriatno
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan.
Harada
Koji
K
Hoque
Mohammad O
MO
Bando
Takashi
T
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009062:Mouth Neoplasms / Q000473:pathology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27