Effects of inducible overexpression of DNp73alpha on cancer cell growth and response to treatment in vitro and in vivo.
The p73 gene has a complex regulation, which leads to the expression of different isoforms, often with opposite biological effects. We have generated in the human colocarcinoma cell line HCT116, expressing a wild-type p53, an inducible DNp73alpha expressing system. Two clones (HCT116/DN3 and HCT116/DN14), upon doxycycline addition, show a strong expression of DNp73alpha. In vitro the two DNp73alpha overexpressing clones grow at similar rate of the control transfected clone (HCT116/8a) and similarly respond to DNA damage. When injected in mice, HCT116/DN3, HCT116/DN14, and HCT116/8a cells grew similarly in the absence or presence of tetracycline. In HCT116/DN3 and HCT116/DN14 tumors, tetracycline induced a strong expression of DNp73alpha both as mRNA and protein. These results indicate that in this system the overexpression of the DNp73alpha does not induce a more aggressive phenotype and does not seem to be associated with a reduced response of the cells to treatment with anticancer agents.
Marabese
M
M
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy. marabese@marionegri.it
Marchini
S
S
Sabatino
M A
MA
Polato
F
F
Vikhanskaya
F
F
Marrazzo
E
E
Riccardi
E
E
Scanziani
E
E
Broggini
M
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D000903:Antibiotics, Antineoplastic; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D004317:Doxorubicin; D004318:Doxycycline