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Role of three cancer "master genes" p53, bcl2 and c-myc on the apoptotic process
1Laboratory of Molecular Biology, University of Florence, Italy.
Abstract:
We review some of the most recent developments concerning three genes involved in human cancer: p53, bcl2 and c-myc. Recent data have demonstrated that the bcl2 gene protects tumor cells from apoptosis induced by a variety of agents, including ionizing radiation, and is thus related to resistance to DNA-damaging therapeutic agents. The p53 tumor suppressor gene, however, has been related with growth arrest, apoptosis and thus with selective sensitivity to the killing effects of ionizing radiation and DNA-damaging drugs. This functional antagonism between the two genes was recently substantiated in molecular terms by demonstration of reciprocal down-regulation due to the presence of a p53-dependent transcription silencer in the untranslated region of the bcl2 gene. Growth arrest in the G1 phase of the cell cycle and induction of apoptosis are two distinct and dissectable functions of p53: bcl2 is able to antagonize the induction of apoptosis by p53, but not the growth arrest in G1. However, coexpression of bcl2 and of the oncogene c-myc efficiently antagonizes effects of p53 on G1 arrest and apoptosis, thus suggesting a cooperation between the two oncogenes. In addition, c-myc disrupts other functions of genetic control in the early G1 phase of the cell cycle including the expression of D1 cyclin. We believe that knowledge of the functional/molecular interactions between these three genes involved in human cancer is a fundamental prerequisite to improve the knowledge on prognosis and to design innovative therapeutic approaches.
Insights
The p53 and bcl2 genes have opposing roles in cancer cell death and growth arrest. Their interaction, along with the oncogene c-myc, influences cancer progression and therapeutic resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p53 tumor suppressor gene and the bcl2 gene play critical roles in human cancer.
- p53 induces growth arrest and apoptosis, while bcl2 promotes tumor cell survival by inhibiting apoptosis.
- These genes are implicated in cellular responses to DNA-damaging agents and therapeutic resistance.
Purpose of the Study:
- To review recent developments on the functional and molecular interactions between p53, bcl2, and c-myc in human cancer.
- To elucidate the antagonistic and cooperative mechanisms governing cell cycle control and apoptosis.
- To highlight the implications for cancer prognosis and therapeutic strategies.
Main Methods:
- Review of recent scientific literature on p53, bcl2, and c-myc.
- Analysis of molecular mechanisms underlying gene interactions.
- Examination of functional antagonism and cooperation in cell cycle regulation and apoptosis.
Main Results:
- bcl2 antagonizes p53-induced apoptosis but not G1 growth arrest.
- A p53-dependent silencer in bcl2 mediates reciprocal down-regulation.
- Coexpression of bcl2 and c-myc overcomes p53's effects on G1 arrest and apoptosis.
- c-myc disrupts cell cycle control, including D1 cyclin expression.
Conclusions:
- Understanding the interplay between p53, bcl2, and c-myc is crucial for cancer prognosis.
- Knowledge of these gene interactions can guide the development of novel cancer therapies.
- The functional antagonism and cooperation among these genes offer potential therapeutic targets.