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  • Title: Role of p53 and apoptosis in carcinogenesis.
    Author: Wang XW.
    Journal: Anticancer Res; 1999; 19(6A):4759-71. PubMed ID: 10697590.
    Abstract:
    Carcinogenesis is a process that converts normal cells from controllable to uncontrollable growth. Coordinate regulation of the rates of cell proliferation and cell death is an important determinant in maintenance of homeostasis. Loss of control of this balance is central to the development of cancer. This loss may be due to genetic alteration in either growth promoting genes resulting in constitutive activation or negative growth regulating genes such as tumor suppressor genes. Recent advances in studying the molecular mechanisms related to the etiology of cancer have provided further understanding of these pathways. Earlier studies have been primarily concerned with cell proliferation resulting from activation of oncogenes. However, many recent studies have focused on the induction of cell death. The recognition of the importance of apoptosis, a distinct mode of cell death, in maintenance of genomic stability was further prompted by studying the mechanism of the tumor suppressor gene product p53, as well as many other oncogenes and tumor suppressor genes. For example, many oncogenes appear to act as potent inducers of apoptosis through activation of p53 dependent apoptosis pathways. Therefore, one possible mechanism for tumor suppression involves activation of apoptosis pathways in cells at risk of neoplastic transformation. These studies have provided extensive knowledge of the signal transduction pathways in response to genotoxic stress and promoted mechanistic research related to the apoptosis pathways. These studies also provide a perfect explanation that p53 is a key element in maintaining genomic stability and loss of the p53 function is a common event during carcinogenesis. This chapter will mainly focus on the role of apoptosis in carcinogenesis. In particular, I will summarize recent studies related to the mechanisms of p53 and its role in this process.
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