Identification and classification of p53-regulated genes

The results revealed substantial heterogeneity in the transcriptional responses to p53, even in cells derived from a single epithelial cell type, and pave the way to a deeper understanding of p53 tumor suppressor action

J. Yu; L. Zhang; P. M. Hwang; C. Rago; K. W. Kinzler; B. Vogelstein

2002

Scholarcy highlights

  • The fact that p53 function is impaired in the majority of human cancers has stimulated efforts to understand the function of this gene in normal and neoplastic states
  • All five cell lines were infected to similar extents, based on green fluorescent protein fluorescence and p53 protein expression assessed by Western blots
  • Initial descriptions of oncogene and tumor suppressor gene action concentrated on relatively simple linear pathways
  • A small number of genes were induced in all of the five lines studied, even by very high levels of p53 expression, despite the fact that the lines were derived from the same precursor cell type
  • The responses to drugs that induce p53 at more physiologic levels were even more heterogeneous. These results suggest that most of the genes transcriptionally activated by p53 are codependent on other transcription factors
  • The presence or absence of such factors is in turn likely to depend on other genetic alterations accumulated during the long history of neoplastic cells before their removal from patients
  • P53 activates the expression of many genes whose effects, in aggregate, determine important components of neoplastic cell behavior

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