Towards an understanding of the role of p53 in adrenocortical carcinogenesis

Mol Cell Endocrinol. 2012 Mar 31;351(1):101-10. doi: 10.1016/j.mce.2011.09.010. Epub 2011 Sep 10.

Abstract

Adrenocortical carcinoma (ACC) is recognized to be a component tumor of the Li Fraumeni Syndrome (LFS), a familial cancer predisposition resulting from germline mutations in the p53 tumor-suppressor. p53 activity is tightly regulated by multiple post-translational mechanisms, disruption of which may lead to tumorigenesis. ACC is present in disproportionately high rates among p53-mutation carriers, suggesting tissue-specific manifestations of p53 deficiency. Additionally, p53-associated ACC demonstrates a strong predominance in infants and children. Several of the p53 alleles associated with pediatric ACC, however, retain significant wild-type activity and demonstrate incomplete penetrance, a finding distinct from other LFS-component tumors. In this review, we discuss the relationship between p53 and adrenocortical carcinogenesis, with specific focus on disease-specific alleles, tumorigenesis in the context of adrenal development and potential therapeutic approaches to p53-associated ACC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Adrenal Cortex Neoplasms* / genetics
  • Adrenal Cortex Neoplasms* / metabolism
  • Adrenal Cortex Neoplasms* / pathology
  • Adrenal Cortex Neoplasms* / therapy
  • Adrenocortical Carcinoma* / genetics
  • Adrenocortical Carcinoma* / metabolism
  • Adrenocortical Carcinoma* / pathology
  • Adrenocortical Carcinoma* / therapy
  • Alleles*
  • Animals
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / metabolism
  • Cell Transformation, Neoplastic* / pathology
  • Child
  • Child, Preschool
  • Humans
  • Infant
  • Li-Fraumeni Syndrome / genetics
  • Li-Fraumeni Syndrome / metabolism
  • Li-Fraumeni Syndrome / pathology
  • Li-Fraumeni Syndrome / therapy
  • Organ Specificity
  • Penetrance*
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53