Effect of p27Kip1 on the ability of invasion and metastasis of an oral cancer cell line.
p27Kip1 is a cyclin-dependent kinase inhibitor which regulates progression of cells from G1 into S phase in a cell cycle. p27Kip1 has been reported to be an important prognostic factor in various malignancies. As the ability of invasion and metastasis has been thought to be the most important factor for patient's prognosis, we examined whether up-regulation or down-regulation of p27Kip1 can affect the ability of invasion and metastasis of an oral cancer cell (B88t cell) in vitro and in vivo. We constructed an expression vector containing sense- or antisense-oriented human p27Kip1 cDNA with pcDNA3.1. We transfected B88t cells with the empty vector, the sense- or antisense-oriented expression vector to regulate the expression of p27Kip1 gene. Up-regulation of p27Kip1 protein markedly inhibited the migration of cancer cells in a Boyden chamber. Down-regulation of p27Kip1 protein markedly enhanced the migration of cancer cells in a Boyden chamber, and the tumor invasion in nude mice. Moreover, we detected up-regulation of E-cadherin and down-regulation of Tiam-1 (tumor invasive and metastasis-1) in the sense transfectants, up-regulation of Tiam-1 and down-regulation of E-cadherin in the antisense transfectants by Western blotting. These results suggest that p27Kip1 may play an important role in the invasion and metastasis of an oral cancer cell involved in regulation of E-cadherin and Tiam-1.
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
Kawaguchi
Shin-ichi
S
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000556:secondary*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015820:Cadherins; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins; D011506:Proteins; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; C513260:Tiam1 protein, mouse; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27