Gene therapy for gliomas: p53 and E2F-1 proteins and the target of apoptosis.
Current therapy for glioma is suboptimal. The transfer of apoptosis genes to tumors constitutes one of the most promising strategies for cancer gene therapy. We have previously shown that massive apoptosis occurs when wild-type p53 or E2F-1 expression is induced in glioma. However, the mechanism of action and the efficiency in inducing apoptosis of these two proteins are not similar. Adenovirus-mediated p53 gene transfer is ineffective in causing apoptosis in glioma cells that retain wild-type p53 genotype or overexpress the p21 protein. The p16/Rb/E2F pathway is the most frequent target of genetic alterations in gliomas, and therefore constitutes a suitable target for gene therapy strategies. However, the transfer of either the p16 or Rb gene to glioma cells results in cytostatic effect. The E2F-1 protein is able to induce generalized apoptosis in gliomas independently of the p53, p16 or Rb status. In addition, p21- or p16-mediated growth arrest did not protect glioma cells from E2F-1-mediated apoptosis. The apoptotic molecule bax is induced in p53-mediated apoptosis, but bax is not induced in E2F-1-mediated apoptosis in glioma cells. Careful selection of patients may be necessary before designing therapeutic strategies using either p53 or E2F-1 as a therapeutic tools for glioma patients.
Gomez-Manzano
C
C
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Fueyo
J
J
Alameda
F
F
Kyritsis
A P
AP
Yung
W K
WK
D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics* / Q000628:therapy; D006801:Humans; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53