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P53 mutations in human cancer
1Cedars-Sinai Medical Center, UCLA School of Medicine 90048.
Abstract:
A 53,000 dalton protein called p53, was noted to be mutated in human cancer in 1987. Further studies have shown that p53 is a tumor suppressor gene which may be one of the most frequently altered genes in cancer of all types. These alterations include interactions with viral antigens, coding mutations and inactivating rearrangements. Accumulating evidence suggests that p53 acts by binding DNA and activating transcription. Expression of p53 after transfection with a constitutive promotor, blocks cellular proliferation and leads to an apoptotic cell death. In normal cells, p53 expression is induced by irradiation; this has led to the hypothesis that p53 acts to inhibit replication during genetic repair. Cells which lack p53 are more prone to develop amplification. Mice lacking p53 are born normal but develop cancer after a lag of months, this suggests that p53 is not an initiating mutation in cancer, but probably a late event.
Insights
The p53 tumor suppressor gene is frequently altered in human cancers. Its inactivation is a late event in cancer development, suggesting a critical role in preventing tumor progression.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The p53 protein, a 53,000-dalton molecule, was identified as mutated in human cancer in 1987.
- p53 is a tumor suppressor gene frequently altered across various cancer types.
- Alterations include interactions with viral antigens, mutations, and rearrangements.
Purpose of the Study:
- To investigate the role of the p53 tumor suppressor gene in cancer development.
- To understand the mechanisms by which p53 functions to prevent tumor formation.
Main Methods:
- Analysis of p53 alterations in human cancers.
- Transfection studies to examine p53 expression and its effects on cellular proliferation and apoptosis.
- Irradiation studies in normal cells to induce p53 expression.
- Studies of p53-deficient mice.
Main Results:
- p53 acts by binding DNA and activating transcription.
- p53 expression blocks cellular proliferation and induces apoptotic cell death.
- p53 expression is induced by irradiation in normal cells, potentially inhibiting replication during genetic repair.
- p53-deficient cells show increased susceptibility to gene amplification.
- p53-deficient mice develop cancer later in life, indicating p53 is a late-acting factor.
Conclusions:
- p53 is a critical tumor suppressor involved in preventing cancer progression.
- Inactivation of p53 appears to be a late event in tumorigenesis.
- Understanding p53's function is crucial for cancer therapy development.