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TAp63gamma can substitute for p53 in inducing expression of the maspin tumor suppressor

Katja Spiesbach1, Andrea Tannapfel, Joachim Mössner

  • 1Department of Internal Medicine II, University of Leipzig, Leipzig, Germany.

International Journal of Cancer
|December 4, 2004
PubMed

Insights

The p63 protein TAp63gamma can activate the maspin tumor suppressor gene, similar to p53. This finding suggests a potential role for p63 in regulating maspin expression within tumors.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cancer Research

Background:

  • Maspin is a tumor suppressor protein inhibiting cellular invasion and motility, and it's part of the serpin family.
  • Maspin gene expression is known to be upregulated by the p53 tumor suppressor protein.
  • The p63 and p73 protein families are related to p53 and were investigated for their role in maspin regulation.

Purpose of the Study:

  • To investigate whether p63 and p73 family proteins can induce maspin expression.
  • To determine if TAp63gamma can substitute for p53 in activating the maspin promoter.
  • To explore the functional significance of p63-dependent maspin upregulation in hepatocellular carcinomas.

Main Methods:

  • Testing the ability of 7 p53-related proteins (p63 and p73 families) to induce maspin expression.
  • Analyzing maspin promoter activation by the p63 splice form TAp63gamma.
  • Using the DLD-1 colorectal adenocarcinoma cell line to observe maspin mRNA and protein level changes upon TAp63gamma induction.
  • Employing immunohistochemistry to examine p53, p63, and maspin expression in hepatocellular carcinoma tissues.

Main Results:

  • The p63 splice form TAp63gamma was found to substitute for p53 in activating the maspin promoter via the same consensus site.
  • Induction of TAp63gamma in DLD-1 cells led to increased maspin mRNA and protein levels.
  • In hepatocellular carcinomas, tumors with mutated p53 often expressed p63 and maspin, suggesting a role for p63 in maspin induction in tumors.

Conclusions:

  • TAp63gamma can functionally replace p53 in the transcriptional activation of the maspin tumor suppressor gene.
  • TAp63gamma utilizes the identical DNA recognition site as p53 for maspin gene activation.
  • Expression patterns in tumor tissues suggest that p63-mediated maspin induction may play a role in cancer progression.

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