Regulation of cell proliferation by induction of p21/WAF1 in rat bladder carcinoma cells using the Cre--loxP system.
p21/WAF1, a cyclin-dependent kinase inhibitory protein, functions as a tumor suppressor. Loss of p21/WAF1 expression has been reported to be an important prognostic predictor in several human malignancies, including bladder carcinomas. In this study, we induced p21/WAF1 using a Cre-loxP gene expression switching vector system in BC31 rat bladder carcinoma cells that feature p53 gene mutations. Cells in which p21/WAF1 was induced in nuclei were not labeled with BrdU and overall showed decreased cell proliferation, with increase in the G0-G1 population evident on flow cytometer analysis. The Cre treatment did not affect BC31 parental cells. These results show induction of p21/WAF1 can inhibit proliferation of tumor cells having p53 mutations, and could thus be applied as a potential therapy.
Ito
Aya
A
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Asamoto
Makoto
M
Hokaiwado
Naomi
N
Shirai
Tomoyuki
T
D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002469:Cell Separation; D004396:Coloring Agents / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics; D005821:Genetic Techniques; D005822:Genetic Vectors; D019426:Integrases / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D045522:Recombinases; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
C493958:Cdkn1a protein, rat; D004396:Coloring Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D045522:Recombinases; D014764:Viral Proteins; C045073:Cre recombinase; D004254:DNA Nucleotidyltransferases; D019426:Integrases; D001973:Bromodeoxyuridine