Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.

Vilgelm AE, Washington MK, Wei J, Chen H, Prassolov VS, Zaika AI
Mol Cancer Ther. 2010 9 (3): 693-705

PMID: 20197393 · PMCID: PMC2838189 · DOI:10.1158/1535-7163.MCT-09-0912

p53, p63, and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation, and other critical cellular processes. Here, we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family rather than p53 alone.

MeSH Terms (23)

Adenocarcinoma Antineoplastic Agents Biomarkers, Pharmacological DNA-Binding Proteins Fluorouracil Gastrointestinal Neoplasms Gene Expression Regulation, Neoplastic HCT116 Cells Humans Multigene Family Multiprotein Complexes Nuclear Proteins Promoter Regions, Genetic Protein Binding Protein Isoforms Stress, Physiological Tissue Array Analysis Trans-Activators Transcription Factors Tumor Cells, Cultured Tumor Protein p73 Tumor Suppressor Protein p53 Tumor Suppressor Proteins

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