Restoration of fragile histidine triad (FHIT) expression induces apoptosis and suppresses tumorigenicity in lung and cervical cancer cell lines
AUTOR(ES)
Roz, Luca
FONTE
The National Academy of Sciences
RESUMO
Loss of expression of the Fhit protein is often associated with the development of many human epithelial cancers, including lung and cervical carcinomas. Restoration of Fhit expression in cell lines derived from these tumors has however yielded conflicting results, prompting the need for careful evaluation of the oncosuppressive potential of FHIT. In the present study, we have investigated the effect of Fhit reintroduction in seven lung cancer and three cervical cancer cell lines. To achieve efficient gene transfer and high levels of transgene expression, we have used an adenoviral vector to transduce the FHIT gene. The induction of apoptosis was evaluated by using the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay and propidium iodide staining. Activation of caspases was detected by using Western blot analysis, and tumorigenic potential of transduced cells in the nude mouse was also assessed. Restoration of Fhit expression induced apoptosis in all Fhit-negative cell lines, with Calu-1, H460, and A549 being the most susceptible among the lung cancer cell lines and SiHa cells among cervical carcinomas. Activation of caspase-8 was always associated with Fhit-mediated apoptosis, and in vivo tumorigenicity was either abolished by FHIT gene transfer (in H460 and SK-Mes cells) or strongly suppressed (in A549 and SiHa cells). Our data demonstrate oncosuppressive properties and strong proapoptotic activity of the Fhit protein in lung and cervical cancer cell lines and strengthens the hypothesis of its possible use as a therapeutic tool.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122572Documentos Relacionados
- Replacement of Fhit in cancer cells suppresses tumorigenicity
- Análise molecular dos genes FHIT (Fragile Histidine Triad) e ATR (Ataxia-Telangiectasia and Rad3 Related) em pacientes com câncer de mama.
- Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines
- Propofol inhibits lung cancer cell viability and induces cell apoptosis by upregulating microRNA-486 expression
- Adenovirus-Mediated p21(WAF1/SDII/CIP1) Gene Transfer Induces Apoptosis of Human Cervical Cancer Cell Lines